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1
Muir, Eric R. "Magnetic resonance imaging of retinal physiology and anatomy in mice." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/37268.
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MRI can provide anatomical, functional, and physiological images at relatively high spatial resolution and is non-invasive and does not have depth limitation. However, the application of MRI to study the retina is difficult due to the very small size of the retina. This thesis details the development of MRI methods to image blood flow (BF), anatomy, and function of the retina and choroid, and their application to two diseases of the retina: diabetic retinopathy and retinal degeneration.
A unique continuous arterial spin labeling technique was developed to image BF in mice and tested by imaging cerebral BF. This method was then applied to image layer-specific BF of the retina and choroid in mice, and to acquire BF functional MRI of the retina and choroid in response to hypoxic challenge. Additionally blood oxygen level dependent functional MRI of the mouse retina and choroid in response to hypoxic challenge was obtained using a balanced steady state free precession sequence which provides fast acquisition, has high signal to noise ratio, and does not have geometric distortion or signal dropout artifacts.
In a mouse model of diabetic retinopathy, MRI detected reduced retinal BF in diabetic animals. Visual function in the diabetic mice, as determined by psychophysical tests, was also reduced. Finally, in a mouse model of retinal degeneration, BF and anatomical MRI detected reductions of retinal BF and the thickness of the retina. The studies detailed in this thesis demonstrate the feasibility of layer-specific MRI to study BF, anatomy, and function, in the mouse retina. Further, these methods were shown to provide a novel means of studying animal models of retinal disease in vivo.
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Fust, Anita. "Lung mechanics in mice : effect of decorin deficiency." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=80268.
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Decorin is required for the normal fibrillogenesis and spatial arrangement of collagen. As collagen is important in determining the elastic behaviour of the lung, we hypothesized that lung tissue mechanics would be altered in decorin deficient (Dcn-/-) mice. Complex impedance, pressure-volume curves, and length-stress curves of lung parenchyma were measured in C57BL/6 mice, 6 Dcn-/- and 6 wildtype ( Dcn+/+), both in vivo and in vitro. Immunohistochemistry and Western blotting were performed to identify decorin and biglycan in the lung tissues. In vivo, airway resistance was decreased and lung compliance was increased in Dcn-/- mice. In vitro, length-stress curves showed increased compliance in the Dcn-/- mice. Immunohistochemistry showed decorin staining in the airway and vessel walls of Dcn+/+ but not Dcn-/- mice; Western blots showed that biglycan levels were not different in the Dcn-/- mice. These data support a critical role for decorin in the formation of the lung collagen network. Lack of decorin alters lung tissue mechanical behaviour. Additionally, the data from Dcn+/+ mice were compared to those from other species, and is consistent with the evidence in the literature that mouse lungs differ structurally from other species. Finally, differences observed in vivo vs. in vitro suggest that measurements made in the strip more accurately reflect lung tissue properties.
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何存邦 and Tsun-bond Horace Ho. "Aldose reductase deficient mice develop nephrogenic diabetesinsipidus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31222663.
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Gobbett, Troy A. "Characterization of phosphofructokinase-M gene expression in preimplantation mouse embryos through the use of competitive reverse transcription-polymerase chain reaction." Virtual Press, 1999. http://liblink.bsu.edu/uhtbin/catkey/1133725.
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The preimplantation mouse embryo undergoes many metabolic changes as development proceeds. One major change is the switch from a pyruvate based metabolism, to a glucose based metabolism. The phosphofructokinase enzyme is the regulatory enzyme of glycolysis and is thought to be a major contributor in controlling the block to glycolysis in early preimplantation mouse embryos. This study was undertaken to construct a system that would allow detection of RNA for the highly glycolytically active subunit (muscletype) of the phosphofructokinase (PFK) enzyme. A muscle specific mutant PFK plasmid was generated to provide mutant internal control RNA. Using this internal control, initial reverse transcriptionpolymerase chain reaction data collected from early embryo stages suggest that the muscle type PFK subunit RNA is not expressed in the preimplantation mouse at the 1-cell or blastocyst stages. This result suggests that PFK activity detected at the later morula and blastocyst stages must be from either a different PFK subunit or a novel embryonic form of PFK.Department of Biology
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Martin, Emily P. "Expression of glutamate dehydrogenase and glutamine synthetase RNA in preimplantation mouse embryos." Virtual Press, 1999. http://liblink.bsu.edu/uhtbin/catkey/1117849.
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Glutamine serves as a major energy source for all stages of preimplantation mouse embryo development, whether the embryos are raised in vivo or in vitro from the one-cell stage. Glutamate dehydrogenase (GDH) and glutamine synthetase (GS) are enzymes that are involved in the metabolism of glutamine. GDH catalyzes the conversion of glutamate into a-ketoglutarate, a primary component of the tricarboxylic acid cycle. GS catalyzes the conversion of glutamate to glutamine. The expression of GDH RNA and GS RNA were analyzed in preimplantation mouse embryos using reverse transcription (RT) with an oligo dT primer followed by Polymerase Chain Reaction (PCR) amplification of GDH and GS cDNAs using gene specific primers. Data show that GDH RNA is expressed in mouse embryos grown in vivo at the one-cell, two-cell, eight-cell, and blastocyst stages of development. GS RNA is not expressed at the one-cell stage, but first appears at the two-cell stage and is expressed at the eight-cell and blastocyst stages. Semiquantitative PCR analysis using a globin internal standard demonstrated that GS RNA is present at high levels at the two-cell stage and declines by 51 % by the blastocyst stage. These results suggest that, within the preimplantation mouse embryo, GDH RNA is expressed by both the maternal genome as well as the embryonic genome, while GS RNA is only expressed by the embryonic genome. This study provides an explanation for why glutamine is utilized as an energy source during preimplantation development, which allows for a better understanding of glutamine metabolism and its role during early mouse development.Department of Biology
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Waclaw, Ronald Raymond. "Expression of cell cycle regulatory proteins cyclin B1, cyclin E, and cdk2 during the first three cell cycles of preimplantation mouse embryo development using indirect immunofluorescence." Virtual Press, 1999. http://liblink.bsu.edu/uhtbin/catkey/1125042.
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The cell cycle is a highly regulated process driven by endogenous factors that have regulatory functions. Certain proteins such as cyclins and cyclin-dependent kinases (cdks) are needed to progress through the four phases of the cell cycle. Cell cycle regulatory proteins have been characterized in somatic cells and exhibit phase specific expression patterns. However, the changes in expression of these proteins have not been characterized in early cleavage stage mouse embryos. This study utilized indirect immunofluorescence microscopy to determine the expression pattern of cell cycle regulators cyclin B 1, cyclin E, and CDK2 during the first three cell cycles of preimplantation mouse embryo development. Results suggest unique and specific patterns of expression for all three cell cycle regulators at different stages of the cell cycle. In G1 of the first cell cycle, cyclin E is expressed at high levels, whereas cyclin B 1 and CDK2 are expressed at moderate levels. During DNA synthesis (S phase), CDK2 levels slightly increase. However, cyclin B 1 and cyclin E levels begin to decline in S and continue to decrease to minimal levels in G2. CDK2 expression follows a similar trend during G2, decreasing considerably. During the second cell cycle, cyclin B 1 and CDK2 show staining patterns similar to the first cell cycle. The expression of cyclin E is maintained at a moderate level throughout the entire second cell cycle. Cyclin B 1, cyclin E, and CDK2 are all expressed at moderate levels during GI of the third cell cycle. During S phase, cyclin B 1 and CDK2 are maintained at moderate levels, but cyclin E is decreased to minimal levels. The expression of all three proteins was minimal during G2. This study provides baseline information on the unique expression patterns of cell cycle regulators in early mouse embryos. The determination of cell cycle protein expression will allow for a better understanding of the complex mechanisms in the division process during preimplantation mouse embryo development.Department of Biology
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Danilovich, Natalia. "Ovarian development and function in follitropin receptor knockout (FORKO) mice." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=37647.
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This dissertation examines the ovarian development and function in genetically modified mice that lack FSH receptor (FSH-R) signaling. We propose that a complete or partial loss of FSH-R causes ovarian insufficiency resulting in estrogen deficiency and premature aging in female mice.Targeted disruption of FSH-R caused a gene dose related endocrine and gametogenic abnormality in female mice. The resulting FOllitropin R&barbelow;eceptor K&barbelow;nockO&barbelow;ut (FORKO) mutants were acyclic and infertile due to ovulatory defects, even with very high levels of FSH. Lack of FSH-R signaling in females caused a severe ovarian underdevelopment, producing estrogen deficiency. As a consequence, the null mutants developed obesity and skeletal abnormalities. The expression of nuclear estrogen receptor(s) alpha and beta genes and the corresponding proteins in the ovary and uterus of FORKO mice were maintained intact, as estrogen administration induced uterine growth and decreased accumulation of the adipose tissue. By 12 months of age, 92% of FORKO animals developed ovarian neoplasms of sex cord-stromal type similar to pathology observed in women. Our results showed, for the first time, that the loss of the FSH-R signaling mechanisms predisposes the ovary to molecular and structural changes causing tumor formation.
In contrast to acyclic and infertile FORKO (-/-) females, a phenotype of FORKO mice with a partial (+/-) disruption of the receptor gene exhibits irregular cyclicity and reduced fertility, undergoing early reproductive senescence. Our findings also demonstrate that the loss of a single allele of the FSH receptor gene causes a premature exhaustion of gonadal reserves accompanied by age-related changes in the hypothalamic-pituitary axis.
The study concludes that the FSH receptor signaling offers a protective mechanism, which gradually weakens upon reproductive senescence (menopause in women); therefore this knockout constitutes a unique and promising animal model for studying the physiology and molecular mechanisms of gonadal receptors and hormones.
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Johnson, Marjorie Isabelle. "Alterations in fast and slow-twitch muscles of genetically dystrophic mice with special reference to parvalbumin." Thesis, University of British Columbia, 1987. http://hdl.handle.net/2429/27358.
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Muscular dystrophy is a genetic disease which affects the morphology, physiology and biochemical nature of the muscle fiber. This study was designed to examine the progressive effects of muscular dystrophy on the differentiation process of skeletal muscle. Chapter 1 examines the neonatal development of muscle spindles and their intrafusal fibers in the soleus and extensor digitorum longus (EDL) of genetically dystrophic mice according to histochemical, quantitative, and ultrastructural parameters. Despite alterations in the surrounding extrafusal fibers, muscle spindles and their intrafusal fibers appeared enzymatically and histologically unaffected in incipient stages of murine dystrophy.
In the second chapter the distribution and concentration of parvalbumin (PV), a calcium-binding protein, in 32 and 2-week-old dystrophic mice was mapped by immunohistochemical and biochemical procedures. The number of parvalbumin-immunoreactive fibers was significantly reduced in the adult dystrophic EDL but slightly increased in the adult dystrophic soleus. No differences between strains were observed in the 2-week samples. These findings were supported by routine myosin ATPase histochemistry. Parvalbumin was isolated on SDS-PAGE gels and the concentration of PV was estimated by a RIA. These results confirmed the immunohistochemical data in that PV content was dramatically reduced in the adult dystrophic EDL and significantly increased in the dystrophic soleus. No changes were detected in the samples of the 2-week-old muscles. The similarity in the distribution and content of PV between the fast and slow dystrophic muscles at 32 weeks of age suggests an alteration in the distribution and phenotypic expression of fiber types in muscular dystrophy and supports the hypothesis that dystrophy alters the normal differentiation process of skeletal muscle.Medicine, Faculty of
Cellular and Physiological Sciences, Department of
Graduate
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許芝盛 and Chi-shing Hui. "The acute and subchronic toxic effects of dichloroacetonitrile inmice." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31970205.
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Siu, Kwan-yin, and 蕭君言. "The development and characterization of a knockout model for secretin." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40887674.
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Newton, Michael John. "The Relationship Between Functional And Histological Changes In Muscle Following Eccentric Exercise In Mice." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2000. https://ro.ecu.edu.au/theses/1529.
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Exercise-induced muscle damage (EIMD) is known to be produced by novel or unaccustomed exercise, especially high force eccentric contractions. Histological myofibre disruption, force loss and muscle soreness are associated with EIMD and have implications for sporting performance. Traditional practices of assessing the extent of disruption to the myofibres is by performing needle biopsies and subsequently analysing the histology of the fibres. Recently there has been interest in investigating whether changes in force production and contractile properties of muscle following damaging exercise correlate strongly with the magnitude of disruption to the myofibres. The main aim of this study was to investigate whether changes in force production and contractile properties of muscle following damaging eccentric exercise correlated with myofibre disruption. In order to test the hypotheses set down in the study 56 mice (C57 BU/10 strain) were randomly assigned to two groups (active and passive). Each main group was then divided into 5 subgroups. Anaesthetised mice performed either 120 active (eccentric contractions) or passive (no muscle contraction) lengthening repetitions after which they were allowed to recover. The right foot was fixed to a foot plate housing a force transducer which was directly attached to the axle of a stepping motor. A stimulating electrode was surgically placed around the peroneal nerve and P. and 1/ 150 Hz ratios were determined. Animals in the active group then performed 5 bouts of 24 stimulated lengthening repetitions at 0.3 amps with a stimulation frequency of IOO Hz. The passive group's protocol was identical with the exception that no stimulation was provided. One repetition for both active and passive groups consisted of a 300 millisecond plantar flexion movement of the foot plate and a 4.7 second dorsi flexion recovery movement to the starting position. Active and passive subgroups were terminated at 3, 6, 10, 15 and 20 days following exercise, prior to which P. and 1/ 150 Hz ratio were determined. Tibialis anterior (TA) muscles were excised at this time from both exercised and contralateral limbs and prepared for later histological examination. Significant differences were evident between the two groups for Po following each bout of 24 lengthening repetitions, 10 minutes following lengthening and on days 3 and 20 of recovery. The only significant differences between the groups in 1/ 150 Hz ratio occurred 10 minutes following lengthening and at day six of recovery (p
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Haddad, Rami. "Gestational diethylstilbestrol impacts adult progeny heart structure, function and gene expression in mice." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=104818.
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Diethylstilbestrol (DES), a potent endocrine disruptor, alters the physiologic function of endogenous steroid hormones. Moreover, the fetus is highly susceptible to epigenetic reprogramming and thus DES exposure in utero is thought to cause epigenetic changes by altering the methylation status of CpG islands in the promoter region of genes. DES was prescribed to pregnant women exposing the fetus and was used in agriculture exposing the general public. Fetal, neonatal and adult cardiomyocytes express estrogen receptors suggesting that DES might impact the heart. Furthermore, calcium-handling genes in cardiomyocytes are regulated by estrogen receptors and thus are subject to epigenetic changes following DES exposure in utero. As a prelude to exposure to environmental endocrine disruptors, we treated pregnant C57bl/6n mice with DES at gestational days 11-14 and examined cardiac structure/function and calcium handling gene expression in adult progeny. We hypothesized that gestational DES alters cardiac structure/function and expression of calcium handling proteins in cardiomyocytes. It was found that gestational DES exposure had an impact on sex ratio and exhibited sex specific differences on gross anatomy (body weight and anogenital distance) of male and female pups at weaning and at adulthood. Furthermore, in utero exposure to DES impacted cardiac structure/function and gene expression of sedentary C57Bl/6n mice in a sex dependent manner. The altered echocardiographic parameters and expression profile of calcium handling proteins of swim exercised DES treated males suggest that they did not remodel normally and could not cope with the physiological stress of swim exercise as well as DES treated females.Diéthylstilbestrol (DES), un perturbateur endocrinien, perturbe le fonctionnement physiologique des hormones stéroïdes endogène. L'ADN génomique est considérablement susceptible à la reprogrammation épigénétique durant le développement du fétus et donc l'exposition du fétus au DES in utero peut causer des changements épigénétiques en modifiant la methylation de l'ADN dans les régions promoteur des gènes. Le DES fut prescrit aux femmes enceintes exposant leur foetus et était utilisée en agriculture exposant le public général. Les cardiomyocytes des fétus, des nouveaux nés et des adultes expriment des récepteurs oestrogéniques suggérant que le DES peut influencer le cœur. De plus, les gènes qui contrôlent l'homéostasie du calcium dans les cardiomyocytes sont régulés par les récepteurs oestrogéniques et donc l'exposition au DES in utero pourrait causer des changements épigénétique dans ces gènes. Pour utiliser l'exposition environnementale des perturbateurs endocriniens come modèle, nous avons exposé des souris C57bl/6n enceinte au DES pendant les jours 11-14 de leur grossesse. Nous avons par la suite examiné la structure et le fonctionnement cardiaque, ainsi que l'expression des gènes qui contrôlent l'homéostasie du calcium dans le cœur. Notre hypothèse suggère que le DES modifie la structure et le fonctionnement cardiaque ainsi que l'expression des gènes qui contrôle l'homéostasie du calcium dans le cœur chez les souris adultes. L'exposition au DES pendant la grossesse a modifié le rapport de ratio de sexe et a induit des différences dans l'anatomie (poids et distance anogenital) entre les deux sexes. De plus, la structure et le fonctionnement du cœur ainsi que l'expression des gènes qui contrôlent l'homéostasie du calcium dans les souris sédentaires on été influencés par l'exposition au DES in utero. Les modifications des paramètres écho-cardiographiques et du profil d'expression des gènes qui contrôlent l'homéostasie du calcium dans les souris males exposées au DES qui ont nagé suggèrent que leur cœur n'a pas remodelé normalement et que les souris males ne pouvaient pas coopérer avec le stress physiologique de la natation autant que les souris femelles exposées au DES.
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Nunn, Nicolas. "The role of the signalling protein XLalphas in cardiovascular control in mice." Thesis, University of Liverpool, 2012. http://livrepository.liverpool.ac.uk/9893/.
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Loss of the signalling protein XLαs in mice leads to a lean phenotype characterised by increased energy expenditure due to elevated sympathetic nervous system (SNS) stimulation of brown adipose tissue. XLαs is the protein produced from the Gnasxl transcript of the imprinted Gnas locus, and has a restricted expression pattern that includes a number of brain regions essential for SNS control of both energy expenditure and the cardiovascular system. However, it is unknown to what degree XLαs influences overall sympathetic tone, or how XLαs signalling in the brain causes these phenotypic changes. Using arterial cannulation, anaesthetised Gnasxl knockout mice had elevated blood pressure, shown to be caused by increased SNS stimulation by a greater blood pressure response to the sympatholytic reserpine in knockouts. Using electrocardiogram (ECG) telemetry, conscious Gnasxl knockout mice had elevated heart rate at night, as well as a significant heart rate response to both reserpine and the parasympatholytic atropine. This supported the previous results showing elevated SNS stimulation of the cardiovascular system, but paradoxically also suggested elevated parasympathetic stimulation. Therefore, autonomic control of the cardiovascular system was investigated in further detail by analysing heart rate variability (HRV). A number of HRV analyses were experimentally validated in wildtype mice. The most reliable method was the fast Fourier transform (FFT); high frequency (HF) power was used as a measure of parasympathetic activity, and low frequency (LF)/HF ratio was used as a measure of sympathetic activity. Gnasxl knockouts had a greater LF/HF response to reserpine, but an equivalent HF response to atropine, suggesting the mice had elevated SNS activity only. Additionally, knockouts had elevated LF/HF ratio at night, suggesting consistently elevated SNS output. Neuronal signalling pathways that may be deregulated in Gnasxl knockouts were investigated by injection of MTII and Exendin-4, agonists to the melanocortin 3/4 and GLP-1 receptors, respectively. Gnasxl knockouts had a hypersensitive heart rate response both to centrally injected MTII in anaesthetised mice and peripherally injected Exendin-4 in conscious mice. The hypersensitivity to Exendin-4 was investigated further by HRV analysis, which showed that Exendin-4 had no effect on the SNS, but caused a potent reduction in parasympathetic activity in both wildtypes and knockouts. Neuronal signalling changes in response to Exendin-4 were investigated by antibody staining for the early response gene c-fos. No significant differences were seen in overall numbers of activated neurones between wildtypes and knockouts in a number of brain regions including the nucleus of the solitary tract (NTS). Interestingly, neurones expressing XLαs showed no c-fos response to Exendin-4, except in the area postrema. In summary, loss of XLαs in mice resulted in elevated SNS stimulation of the cardiovascular system, as well as hypersensitivity to Exendin-4 that was unlikely to be caused by increased activation of XLαs-deficient neurones.
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Farmer, Brandon. "Effects of Microgravity on Mucin Production in the Urinary Bladder in Mice." Digital Commons @ East Tennessee State University, 2012. https://dc.etsu.edu/honors/137.
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The effects of the microgravity of spaceflight are largely unexplored with regard to biological tissues. One particular area of interest is the possible effects microgravity could have on the production of mucins. To determine the possible effects of microgravity on mucin production in the urinary bladder, we examined the transitional epithelium of the urinary bladder from female mice that were flown on the space shuttle Endeavour for 12 days in August, 2007. The flight tissue was compared to tissues from two control groups of animals, ground control and baseline. This study utilized three sets of female mice, with each set consisting of 12 animals. The three sets were designated as Flight, Ground Control, and Baseline. The flight animals were flown in the Commercial Biomedical Testing Module-2 (CBMT-2) which was housed in the shuttle’s mid-deck locker area. Ground control animals were also housed in CBTM-2 units which were kept in environmentally controlled rooms at the Space Life Sciences Lab at Kennedy Space Center. Baseline animals were also housed at the Space Life Sciences Lab but were housed in standard rodent cages with ambient temperature and humidity, with a 12/12 light dark cycle. Bladder tissue was paraffin embedded, sectioned, mounted, and histologically stained using an Alcian Blue Periodic Acid Schiff staining procedure. The bladder tissue from the three treatment groups is being qualitatively analyzed for mucin thickness and types of mucins produced. To date the study indicates that the mucin layer of the Flight tissue is thinner than that of the Baseline or Ground Control tissue, but only significantly thinner than the Baseline tissue.
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Urrutia, Maria Soledad. "Direct and correlated responses to selection for weight gain in mice." Thesis, McGill University, 1985. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=72052.
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Direct and correlated responses to selection for weight gain were investigated after nine generations of within family selection. Four selection criteria were used: gain between 28 and 38 or 48 and 58 days of age, and under two feeding regimes, ad libitum consumption or restricted to 80% of control lines. Two lines consisting each of twenty pair matings were selected under each of these criteria. Two unselected control lines were kept. Carcass composition analyses were performed in generation nine at the beginning and end of each selection period and at 100 days of age.Direct responses to selection in the first period were greater in the ad libitum lines while in the second period direct responses were greater in the restricted lines. Direct responses and realized heritability estimates were significantly different between the sexes; males had greater direct responses and higher heritabilities in all selected lines. Body weights before the selection periods decreased in all lines as a result of selection. Body weights after the selection period were not different from controls in the ad libitum lines while restricted lines remained smaller animals. Correlated responses in feed efficiency and feed consumption in the ad libitum lines were positive in the first period and negative in the second period. Restricted lines had a positive response in feed efficiency and negative response in consumption in both periods of selection. Changes in body composition in the first period reflected the changes in body weights through a lower crude protein percentage at the start of the period and a lower ash percentage at the end of the period. Body composition at the start of the second period was not altered by selection, while at the end of the selection period ad libitum lines had higher dry matter percentages and restricted lines had lower fat percentages. Body composition at 100 days of age was not affected by selection except for dry matter percent, that was lower in the restricted lines.
Correlated response in fitness was evaluated through litter size. In the first period lines selected under ad libitum feeding were not affected by selection for increased weight gain while selection for weight gain under restricted feeding caused a significant decrease in litter size.
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Simeone, Stefania. "Gene expression in the vasculature of mice overexpressing human endothelin-1 in the endothelium." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86854.
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Endothelin-1 (ET-1), an endothelium-derived vasoconstrictor peptide, plays a role in the pathophysiology of cardiovascular disease. Transgenic mice that overexpress human preproET-1 selectively in the endothelium exhibit endothelial dysfunction and hypertrophic remodeling of resistance-size arteries in the absence of blood pressure elevation. In order to understand the mechanisms whereby ET-1 directly induces vascular damage, we determined the changes in gene expression in mesenteric arteries of these mice using genome-wide expression profiling. This study revealed a set of genes potentially regulated by ET-1, which might be implicated in ET-1 induced-vascular damage. Our findings suggest that increased endothelium-restricted ET-1 expression results in early changes in gene expression, which increase lipid biosynthesis and decrease bone morphogenetic protein (BMP)-4 expression, and may contribute, at least in part, to ET-1-induced vascular damage. These results have the potential of defining ET-1 gene targets, which may facilitate the discovery of new therapeutic approaches against detrimental effects of ET-1.Keywords: endothelin-1, gene expression, lipid biosynthesis, BMP4
L'endothéline-1 (ET-1), un puissant peptide vasoconstricteur produit par l'endothélium, joue un rôle dans la pathophysiologie des maladies cardiovasculaire. Des souris transgéniques surexprimant la prépro-ET-1 humaine dans l'endothélium présentent une dysfonction endothéliale et un remodelage hypertrophique des artères de résistance en l'absence d'hypertension. Pour comprendre les mécanismes expliquant les modifications vasculaires de ces animaux, nous avons étudié les changements transcriptomiques dans les artères mésentériques. Cette étude a révélé une série de gènes régulés par l'ET-1 qui pourrait être impliquée dans les dommages vasculaires induits par l'ET-1. Ces résultats suggèrent qu'une augmentation d'expression d'ET-1 augmente la biosynthèse de lipides et diminue l'expression de la « bone morphogenic protein » (BMP)-4, ce qui pourrait contribuer, du moins en partie, aux développements des dommages vasculaires induits par l'ET-1. Ces résultats ont le potentiel de définir des cibles de l'ET-1 qui pourraient faciliter la découverte de nouvelles approches thérapeutiques contre les effets nuisibles de l'ET-1.
Mots clés: endothéline -1, changements transcriptomiques, biosynthèse de lipides, BMP4
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Xia, Zhunan. "In vivo study of the physiological role of acylation stimulating protein in mice." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85106.
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ASP acts as a paracrine and autocrine signal to increase triglyceride synthesis in adipocytes. ASP administration results in more rapid postprandial lipid clearance. This present work consists of a series of experiments on complement C3 knockout mice (therefore ASP deficient mice) in vivo. The aim of this work is to understand the role of Acylation stimulating protein (ASP) in energy regulation.Compared to wild type mice, ASP deficient mice have delayed triglyceride and fatty acid clearance, decreased fat mass and body weight with concurrent increases in food intake. Both male and female ASP deficient mice have increased oxygen consumption, an indication of increased energy expenditure. This effect was not dependent on the presence of leptin. On the other hand, the mechanism of increased energy expenditure was different in male and female ASP deficient mice. Female ASP deficient mice have increased movement while the male ASP deficient mice were found to have increased uncoupling protein-3 expression in muscle. Fat load tests in the male mice demonstrate ASP deficiency redirects absorbed energy from storage in adipose tissues towards utilization in liver and muscle. Acute administration of ASP normalizes this process.
The results from these studies suggest that ASP is a key hormone regulating lipid storage in adipocytes. Deficiency of ASP leads to energy repartition, decreased energy storage and increased energy expenditure. In short, ASP deficiency results in obesity resistance.
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Iñiguez, Sergio Diaz. "The effects of acute posttraining injections of cocaine on spatial memory in C57BL/6 mice." CSUSB ScholarWorks, 2007. https://scholarworks.lib.csusb.edu/etd-project/3244.
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The purpose of this study was to investigate the effects of cocaine on spatial memory consolidation using the Morris water maze. Specifically, male and female C57BL/6 mice were trained on a spatial water task, and then administered a single posttraining injection of saline or cocaine (1.25, 2.5, 5.0, or 20.0 mg/kg).
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Hogg, Paul Sumpter. "The Effects of Exogenous Triiodothyronine on Reproductively Inhibited Prairie Deer Mice (Peromyscus maniculatus bairdii) from Laboratory Populations." W&M ScholarWorks, 1989. https://scholarworks.wm.edu/etd/1539625505.
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何仲賢 and Chung-yin Maggie Ho. "The functional role of endothelin-1 in astrocytes by making use of endothelin-1 knockout mice." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31222584.
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Chung, Chi-kin Samuel, and 鍾志堅. "The development and characterization of a gene-knockout mouse model for secretin receptor." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B45014759.
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Welman, Shaun. "Seasonal changes in the heat production of an African small mammal, Rhabdomys pumilio." Thesis, Nelson Mandela Metropolitan University, 2012. http://hdl.handle.net/10948/21417.
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Endothermy refers to the ability of an individual to produce heat from internal sources, and allows animals to maintain a body temperature that is higher than their external environment. Although much is known about the benefits of endothermy, its origin is highly debated. Nonetheless, due to environmental variation, endotherms have to regulate their heat production (thermogenesis) in order to remain normothermic. An endotherms regulatory response seems to be body size dependent. Keeping warm during cold periods is energetically expensive, and for small mammals this is exacerbated by their high rate of heat loss due to high surface area to volume ratios. To compensate for the heat lost, small non-hibernating mammals must increase their level of thermogenesis. Much of our current understanding of thermogenic responses of small mammals is derived from laboratory acclimated animals, and studies on naturally acclimatized animals are uncommon. In addition, most studies on thermogenesis tend to focus on one level of animal organisation, such as subcellular, tissue or in-vivo, but seldom integrate these data. The aim of this study was to measure year-round variation in thermogenesis across all levels of organisation, using naturally acclimatized Rhabdomys pumilio individuals from the Nelson Mandela Metropolitan University, Port Elizabeth. It was predicted that the level of thermogenesis would be significantly higher during winter relative to other seasons in order to cope with the low ambient temperatures (Tas) experienced during this season. Open flow respirometry was used to measure the animal's oxygen consumption, as a proxy for metabolism; the by product of which is heat production. The animal's basal metabolic rate (BMR), nonshivering thermogenesis (NST) capacity and summit metabolic rate (MSUM) were measured. A Western blot analysis was used to determine the expression of uncoupling protein 1 (UCP 1) in the animals' brown adipose tissue (BAT), as well as determine its relative concentration. The cytochrome c oxidase (COX) activity of the animals' visceral organs and BAT was measured, as an indicator of the tissues' metabolic activity. COX activity was determined as the difference in the tissues' oxygen consumption before and after the addition of horse cytochrome c.
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Kongmanas, Kessiri. "Significance of sulfogalactosylglycerolipid in male fertility: Studies using Cgt heterozygous mice." Thesis, University of Ottawa (Canada), 2008. http://hdl.handle.net/10393/27996.
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Sulfogalactosylglycerolipid (SGG) is a sulfoglycolipid present specifically at a substantial level in mammalian male germ cells. It has been shown to function as an adhesion molecule important for sperm-egg interaction and a structural lipid involved in formation of sperm lipid rafts during capacitation in vitro. Due to the unique characteristics and functions, SGG can potentially serve as a biomarker for sperm fertility as well as a target for development of a non-hormonal contraceptive. To confirm the in vivo roles of SGG, we sought for transgenic mice with reduced amounts of sperm SGG. Cgt knockout male mice, transgenetically deficient in UDP-galactose:ceramide galactosyltransferase (CGT), an enzyme involved in SGG synthesis, are infertile due to spermatogenesis disruption. However, the Cgt+/- males can still produce sperm and sire offspring. We hypothesized that Cgt+/- males, expected to have reduced SGG amounts, would have compromised fertilizing ability and could serve as in vivo models for studying roles of SGG in fertilization and spermatogenesis. Unexpectedly, our results revealed that Cgt+/- males exhibited unimpaired spermatogenesis and fecundity. Moreover, the levels of SGG as well as lipid profiles of sperm and testes of Cgt+/- mice were similar to those of the wild type, suggesting that compensatory mechanisms must have occurred to maintain SGG levels in the Cgt+/- mice. Although these results revealed that Cgt+/- mice could not be used as the animal models, they implicated significance of normal testis and sperm SGG levels in maintaining normal spermatogenesis and fertility. The possible compensatory mechanisms regulating SGG levels were further investigated in Cgt+/- mice. As expected, only half of Cgt mRNA expression level of the wild type was transcribed in the Cgt+/- testes; however, testicular CGT polypeptides as well as their enzymatic activities in the Cgt+/- mice were found at a comparable level to those of the wild type. On the other hand, no change was found in terms of mRNA levels, polypeptide levels or enzymatic activities of arylsulfatase A (ASA), the enzyme responsible for SGG degradation in the testis. In conclusion, the compensatory mechanisms for SGG level adjustment in Cgt +/- mice occurred through the biosynthetic pathway, rather than the degradation pathway, by increasing the CGT polypeptide expression level. Therefore, identification of specific spermatogenic cell stages, contributing to normal expression levels of CGT and SGG in the Cgt+/- testes warrants further studies, as these studies should provide useful information regarding CGT and SGG importance during male germ cell development. In addition, a new approach to produce the animal models that can produce sperm with reduced SGG levels should be attempted. The RNA interference (RNAi) techniques may be tried to achieve this goal.
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Thompson, Lucinda Jenny School of Biotechnology & Biomolecular Sciences Microbiology & Immunology UNSW. "Use of microarray technology to study the physiology and pathogenesis of mouse colonising strains of Helicobacter pylori." Awarded by:University of New South Wales. School of Biotechnology and Biomolecular Sciences, Microbiology and Immunology, 2003. http://handle.unsw.edu.au/1959.4/19314.
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Helicobacter pylori is a unique bacterial pathogen which colonises the human stomach. Infection with H. pylori has been linked to several disease outcomes including gastric and duodenal ulcer, gastric cancer and MALT lymphoma. Considering the harsh environment in which it resides and the lack of competition from other bacteria, this host/pathogen relationship is particularly interesting. Microarray analysis is a new and powerful technique which can be used to investigate various aspects of these complex interactions. Expression profiling of bacteria using microarrays remains in its infancy and thus appropriate methods were developed herein for investigating the transcriptional responses of H. pylori to various environments in vitro. Studies showed the tight relationship between growth phase dependent expression of iron homeostasis, motility and virulence genes in H. pylori for the first time. Consequently, the late exponential phase of growth was implicated as the most virulent growth phase of this bacterium in vitro. In response to mammalian cell co-culture, induced expression of H. pylori metabolism/respiration genes, genes of unknown function and genes encoding the 2-component regulators, HP1021 and HP0166, were detected. These represent a set of genes likely to be important specifically in the context of infection. To investigate the host response to infection a new mouse colonising strain of H. pylori, the Sydney Strain 2000 (SS2000), was isolated for use in comparative studies with the established strain, Sydney Strain 1 (SS1). Both host and strain specific effects were studied in a 15 month colonisation experiment using C57BL/6 and BALB/c mice. Genomic typing was used to investigate dynamic changes that occurred in the mouse-adapted strains during colonisation. In these animals reponses relating to the severity of inflammation and to the infecting H. pylori isolate were revealed by gene expression profiling. Previously unrealised cellular responses were uncovered. These included the significant down-regulation of both ferritin and haemoglobin expression. This perhaps suggests a mechanism for H. pylori induced iron deficiency anaemia. Physiological connections between colonisation, acid secretion and expression of the endocrine hormones were also implicated. These experiments have shown the utility of microarray analysis in the investigation of pathogenesis and have highlighted many directions for further investigation.
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Sanders, Theresa A. "Quantitation of Teratogenic Effects of 5-fluorouracil Administered to Mice in Vivo or in Submerged Limb Culture." Digital Commons @ East Tennessee State University, 1987. https://dc.etsu.edu/etd/2786.
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This study demonstrates the use of submerged limb culture in teratologic testing. Pregnant mice were treated on day 11 of gestation (E11, plug date = E0) with 10, 20 or 40 mg of 5-fluorouracil (FU) per kg body weight. On E17, treated and untreated fetuses were examined for gross malformations and were fixed in 95% ethanol. Reduction of limb size and digital defects, including ectrodactyly (ED), syndactyly (SD), microdactyly and polydactyly were dose-dependent. In parallel studies, pregnant mice were treated on the morning of E11 and embryos were removed either 7h (E11) or 24h (E12) later for submerged limb culture. Changes in limb area showed a dose-response relationship while treatment had little effect on the shape of individual bones. This indicates the relatively unspecific nature of FU-induced embryotoxicity. E11 studies revealed a dose dependent response of ED, SD and fusion of the metacarpals/metatarsals (MC/MT) to the proximal phalanges. Unlike E11 cultures, middle phalanges were present but decreased in number as dosage increased. Limbs from embryos of untreated females were cultured (E11) in the presence of 0.002, 0.02, 0.2 or 2.0 mg FU/ml culture medium. The percentage of limbs void of paw cartilage or with decreased numbers of MC/MT was dose-dependent. A dose-dependent decrease in the deleterious effects of 0.02 mg FU/ml was observed when 0.2 or 0.02 mg thymine/ml was added to the cultures. In both culture and non-culture studies, hindlimbs (HL) were more affected than forelimbs (FL) and distal regions were more affected than proximal ones. In addition to the morphometric analyses, biochemical parameters of growth and differentiation were examined at 0, 36 and 72h of culture in untreated and treated limbs. Both DNA and protein of FU treated limbs were decreased compared to untreated controls. FL demonstrated greater capacity for regulation of losses in protein content, HL for DNA content. Submerged limb culture provides a useful model for the examination of xenobiotic effects on limb development and allows some comparative evaluation among in vivo, in vivo/in vitro and in vitro studies. (Abstract shortened with permission of author.)
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Saleh, Jumana. "Acylation stimulating protein : production, receptor interaction and role in vivo in humans and mice." Thesis, McGill University, 1998. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=35938.
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This work has focused on understanding in vivo aspects of ASP metabolism particularly postprandially. I showed that ASP was produced directly from human adipose tissue, a process that increased postprandially and was correlated with increased plasma triglyceride clearance and increased fatty acid incorporation into adipose tissue "FIAT". The target of ASP is adipose tissue. Binding studies in freshly obtained adipose tissue demonstrated specific binding to high affinity receptor sites. ASP binding to subcutaneous tissue from obese females demonstrated the greatest binding and highest receptor affinity. In contrast omental tissue particularly from males showed the lowest specific binding and affinity. This suggests an important role for ASP in maintaining regional adipose tissue mass in females and males, hence providing possible explanations for the metabolic complications seen in abdominal obesity.The strongest evidence for a physiological role of ASP on triglyceride clearance for ASP in vivo was obtained when exogenous intraperitonial hASP was administered to genetically obese mice. Normolipidemic ob /ob mice demonstrated accelerated postprandial TG clearance in the presence of ASP. The effect in the hyperlipidemic: db/db mice, however was markedly greater (2 to 8 times). These findings strongly support the hypothesis that ASP is an important factor in postprandial lipid metabolism and may be a significant factor in determining the pathophysiology of obesity and related dyslipidemias.
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Maimaniee, T. A. "Impact of varied diets on some aspects of behaviour and physiology in laboratory mice." Thesis, Swansea University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.637981.
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The impact of dietary fats was assessed in Swiss mice of differing ages (juvenile and adult) and sexes for two periods (3 and 6 weeks). Mice were fed four specially-formulated pelleted diets containing respectively 8% saturated vegetable fat, 8% soya oil, 8% olive oil and 2% soya oil (with identities hidden from the experimenter) or a local commercial chow. Subjects were individually housed in traditional cages or in metabolism cages to assess daily food consumption and body weight changes over the experimental period. Traditionally-caged mice were also assessed under red lighting for behaviour in a modified 'open field' (a 30 x 20 cm box with a black floor). Videotaped records were analysed using 'The Observer' system quantifying transitions between inner and outer areas, rearing, freezing, grooming and defaecation as well as location in the two equal-sized zones. Measures were factor analysed to facilitate interpretation. Other subjects were used to assess core body temperatures as well as a range of blood (cholesterol, triglycerides and glucose) and plasma (high density lipoprotein cholesterol) measures. Animals in metabolism cages were used to determine daily production of dried faecal material and urine in response to the diets. Clearly, these non-isocaloric diets differed in palatabilities, producing complex effects on growth as well as physiological and behavioural measures. Many indices were influenced by age, sex, duration of dietary exposure and the type of caging used. Interactions between factors were common. Defaecation does not seem to provide a useful index of 'emotionality' in this type of study. Investigations lacking a wide range of indices are unlikely to provide unequivocal support for postulated links between dietary lipids and behaviour. The thesis broadly supports the contention that dietary fats subtly influence mood in mice and differentially influence blood cholesterol values and other factors relevant to coronary heart disease risk in humans.
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Hamade, Bachar. "Fracture repair in Cyp24a1 deficient mice: biomechanical properties of repaired bones and contribution to mechanisms involved." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119501.
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Vitamin D is a key modulator and regulator of mineral and bone homeostasis. The main active form of vitamin D in the body is the 1,25-(OH)2D metabolite that is formed in the kidney from 25-(OH)D by the enzyme CYP27B1. The enzyme CYP24A1 initiates the C24-oxidation pathway that leads to degradation of the hormonal form of vitamin D, but is also responsible for the synthesis of 24,25-(OH)2D. The putative biological activity of 24,25-(OH)2D remains unclear, but it has been found that following tibial fractures in chicks, the levels of CYP24A1 activity and serum 24,25-(OH)2D are both elevated. Our laboratory has engineered a mouse deficient for the Cyp24a1 gene to study the role of 24,25-(OH)2D, and has identified a putative membrane receptor (FAM57Bv2) to 24,25-(OH)2D. In this study we assessed the biomechanical properties (stiffness and force needed to break) of the repaired bones of mutant and wild-type mice at different intervals in the presence or absence of treatment with exogenous 24,25-(OH)2D. We also assessed the mRNA and protein expression of the putative receptor in different organ tissues of wild-type mice. Methods: wild-type and Cyp24a1-deficient mice were subjected to a modified open osteotomy with subsequent intramedullary nailing of the tibia, followed by subcutaneous treatment with vehicle (propylene glycol) or 6.7 µg/kg of 24,25-(OH)2D. Tibiae were collected on days 18 and 28 post operatively, and the biomechanical properties were tested using a three point bending testing machine. To assess the mRNA and protein expression of Fam5bv2 in different tissues, qRT-PCR, western blot analysis and immunohistofluorescence were performed. Results: at day 18, we observed significantly inferior biomechanical parameters in the male and female mutant mice injected with vehicle compared to their wild-type littermates. These differences were rescued by exogenous administration of 24,25-(OH)2D. No statistically significant differences were measured at day 28. qRT-PCR analysis showed high mRNA expression of Fam57bv2 in skin and cartilage, while western blot analysis showed FAM57B (all isoforms) to be expressed in all tissues studied. Immunohistofluorescence studies showed detection of FAM57B in brain paraffin sections, and kidney and tibial cryosections. Conclusion: The results of this study confirm the delay of fracture healing in Cyp24a1-deficient mice and support a role for 24,25-(OH)2D in optimizing fracture healing. Our expression monitoring results show that the putative receptor for 24,25-(OH)2D, FAM57Bv2, is broadly expressed with enrichment in chondrocytes, which may contribute to improved fracture healing.La vitamine D est un modulateur clé de l'homéostasie des minéraux. La forme active de la vitamine D est la 1,25-(OH)2D synthétisée au niveau du rein par l'action de l'enzyme CYP27B1 sur le précurseur 25-(OH)D. L'enzyme CYP24A1 initie la voie d'oxydation C24 qui conduit à la dégradation de la forme hormonale de la vitamine D, mais est également responsable de la synthèse de 24,25-(OH)2D. L'activité biologique de la 24,25-(OH)2D demeure controversée, mais il a été constaté qu'à la suite de fractures du tibia chez les poussins, les niveaux d'activité de la CYP24A1 et les niveaux sériques de 24,25-(OH)2D sont stimulés. Notre laboratoire a mis au point une lignée de souris déficientes pour le gène Cyp24a1 afin d'étudier le rôle de la 24,25-(OH)2D, et a identifié une molécule qui pourrait agir comme récepteur membranaire pour la 24,25-(OH)2D (FAM57B2). Dans cette étude, nous avons évalué les propriétés biomécaniques (rigidité et la force maximale pour rompre) des os réparés chez des souris mutantes et de type sauvage, suite à un traitement en présence ou absence de 24,25-(OH)2D exogène. Nous avons également évalué l'expression de l'ARNm et de la protéine du récepteur putatif dans différents organes chez les souris sauvage. Méthodes: les souris de type sauvage ou déficiente pour le gène Cyp24a1 ont été soumise à une ostéotomie ouverte modifiée du tibia avec insertion d'un clou médullaire, suivie d'un traitement sous-cutané avec le véhicule (propylène glycol) ou avec 6,7 g/kg de 24,25-(OH)2D. Les tibias ont été prélevés aux jours 18 et 28 suivant la chirurgie, et les propriétés biomécaniques ont été testées en utilisant un test de flexion à trois points. Pour évaluer l'ARNm et l'expression de la protéine de Fam57bv2 dans différents tissus, une amplification par PCR quantitative, l'immunobuvardage et l'immunohistofluorescence ont été utilisés. Résultats: au jour 18, nous avons observé que les paramètres biomécaniques sont nettement inférieurs chez les souris mutantes mâles et femelles injectées avec le véhicule par rapport aux animaux de type sauvage. Ces différences disparaissent suite à l'administration de 24,25-(OH)2D exogène. Aucune différence statistiquement significative n'a été mesurée au jour 28. L'analyse qRT-PCR a montré une expression elevée de l'ARNm de Fam57bv2 dans la peau et le cartilage, tandis que l'analyse par immunobuvardage a montré que FAM57B (toutes les isoformes) est exprimée dans tous les tissus étudiés. L'immunohistofluorescence a permis de détecter FAM57B dans des coupes en paraffine de cerveau et dans des cryosections de rein et de tibia. Conclusion: Les résultats de cette étude confirment le retard de la guérison des fractures chez les souris déficientes en Cyp24a1 et soutiennent un rôle de la 24,25-(OH)2D à optimiser la guérison des fractures. Nos résultats concernant l'expression de FAM57B montrent que le récepteur potentiel de la 24,25-(OH)2D, FAM57Bv2, est exprimé à des niveaux élevés dans les chondrocytes, ce qui appuie une contribution mécanistique au cours de la guérison des fractures.
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Turnock, Margaret Elizabeth. "Effects of stress and intra-uterine position on reproductive function in female mice." Thesis, Keele University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385556.
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Kates, Anna-Lisa. "Thyroid hormone metabolism in brown adipose tissue of lean and genetically obese (OBOB) mice." Thesis, University of Ottawa (Canada), 1989. http://hdl.handle.net/10393/21547.
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Regnier, Shane Michael. "Dietary and developmental exposure to the fungicide tolylfluanid disrupts global energy metabolism in mice." Thesis, The University of Chicago, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=3718548.
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The past several decades have witnessed a dramatic expansion in the rates of metabolic disease, most prominently the obesity and diabetes epidemics. While metabolic disease is undoubtedly driven by increased caloric intake and decreased physical activity, exposure to endocrine disrupting chemicals (EDCs) has been implicated as a causal factor in the development of metabolic disease. EDCs are exogenous compounds capable of modulating endogenous hormonal axes, with some compounds capable of interfering with metabolic pathways. Prior work identified the fungicide and booster biocide tolylfluanid (TF) as a potent EDC with the capacity to induce adipocyte differentiation and impair adipocyte insulin signaling through stimulation of the glucocorticoid receptor (GR). The present studies seek to expand upon these data by investigating the outcomes of dietary exposure to TF across the lifespan, with the hypothesis that TF disrupts energy metabolism through aberrant stimulation of the GR, and that disruptions in global metabolic homeostasis are driven by modulation of adipose physiology. When male mice were provided a diet supplemented with 100ppm TF, they exhibited several metabolic changes that mirror the metabolic syndrome, including augmented visceral adiposity, glucose intolerance, global and cellular insulin resistance, and disruptions in circadian rhythms. Importantly, gene set enrichment analysis identified an enrichment of GR-dependent genes in the adipose tissue of exposed mice. Next, investigating the interaction of TF with diet identified novel differences in the outcomes of exposure depending on the background macronutrient content of the diet. Finally, developmental exposure to TF during prenatal and early postnatal life was found to modulate insulin-glucose homeostasis in adult life, in a sex-dependent manner. Taken together, these findings identify TF as a novel metabolic disruptor in vivo, and support prior studies identifying TF as a potent environmental glucocorticoid.
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Vaccarino, Anthony Leonard. "Naloxone analgesia in BALBc mice : a dose-dependent relationship." Thesis, McGill University, 1987. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66239.
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Monemdjou, Shadi. "Metabolic control and regulation of mitochondrial proton leak: Effects of UCP1 deficiency and aging in mice." Thesis, University of Ottawa (Canada), 1998. http://hdl.handle.net/10393/4293.
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The overall objective of this thesis was to examine various aspects of the metabolic significance and regulation of the mitochondrial proton leak. The research conducted specifically assesses the influence that leak has on age-associated changes in mitochondria, and the role that the leak plays in facultative energy expenditure of transgenic mice which lack uncoupling protein-1 (UCP1), a well known mediator of the proton leak. Proton leak in mitochondria has been studied for over ten years, but its exact mechanism has not yet been elucidated and only recently has it been realized that it might be mediated by uncoupling proteins (UCPs). UCPs may confer a mechanism for proton leakage and thus affect the efficiency of oxidative phosphorylation. Mice deficient in the gene for mitochondrial UCP1 (Ucp1-deficient mice) are cold-sensitive despite their abundant expression of genes for the isoforms (Ucp2 and Ucp3), and do not become more obese than controls when fed a high fat diet (Enerback et al. 1997) The objective of our work was to analyse the metabolic control and characteristics of proton leak in mitochondria from brown adipose tissue (BAT) of Ucp1-deficient mice and of heterozygote controls in order to establish the role of the UCPs in facultative thermogenesis. (Abstract shortened by UMI.)
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Al-Fadda, Assim. "Metabolic consequences of deleting the mitochondrial glycerol-3-phosphate dehydrogenase gene in mice." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=80162.
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To define the role of mitochondrial glycerol-3-phosphate dehydrogenase (EC 1.1.99.5; mGPD) in energy balance and intermediary metabolism, we studied female transgenic mice lacking the mGPD gene (mGPD-/-). These mice had higher serum glycerol and triglycerides; lower body weight, blood glucose, and energy expenditure (QO2); and higher glycerol-3-phosphate and lactate/pyruvate ratio in muscle than controls with wild type genotype (WT). When given a high fat/low carbohydrate diet, mGPD-/- mice gain more weight than WT, without the genotype differentially affecting QO2 or calorie intake. On a low fat/high carbohydrate diet, mGPD-/- mice failed to increase QO2 as the WT and gained more weight. After a 30-hour fasting or food restriction to 70% for 10 days, WT lost significantly more weight than mGPD-/- mice, but these latter had lower body temperature and QO2. Thus, mGPD-/- mice exhibit a thrifty phenotype largely resulting from reduced obligatory thermogenesis.
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Cheung, Hiu-wing, and 張曉穎. "Role of p75 neurotrophin receptor in neonatal mouse hypoxic ischemic encephalopathy." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31227247.
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Turri, Maria Grazia. "Mapping of behavioural quantitative trait loci." Thesis, University of Oxford, 2002. http://ora.ox.ac.uk/objects/uuid:89823fa1-c1d3-49e3-acb9-46da18b12245.
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Anxiety is a common disorder which affects about 25% of the population and whose pathophysiology is still poorly understood. Animal models of disease have been widely used to investigate the molecular basis of human disorders, including psychiatric illnesses. This thesis is about the study of the genetic basis of a mouse model of anxiety. I have carried out a QTL mapping study of behavioural measures thought to model anxiety. I report results from 1,636 mice, assessed for a large number of phenotypes in five ethological tests. Mice belonged to two F2 intercrosses originated by four lines generated in a replicate selection experiment. By comparing mapping results between the two crosses, I have demonstrated that selection operated on the same relatively small number of loci in the four selected lines. Analysis of genetic effect of QTL across phenotypes has allowed me to identify loci with specific roles on different dimensions of anxious behaviour, therefore enhancing our understanding of the anxiety phenotype in mice. For some of these QTL I have also accomplished fine mapping experiments: a locus on chromosome 15 is now contained in an interval of only 3 centimorgans. This work is the basis for further molecular dissection of the genetic loci that underlie anxiety and provides a starting point for the discovery of genes involved in a common psychiatric condition.
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Simion, Oana-Maria. "Uncoupling proteins mRNA levels in mice lacking acylation-stimulating protein." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33018.
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The etiology of obesity involves imbalanced energy intake and utilization. ASP is an adipose tissue hormone that facilitates adipocyte uptake of serum fatty acids and their storage. Mice lacking ASP have less adipose tissue mass, despite increased food intake, than wild-type littermates. We hypothesize that the unstored fuels are oxidized through UCP (thermogenic mitochondrial carriers).In male ASP-deficient mice mRNA levels were measured by semi-quantitative RT-PCR and the following changes were observed: UCP-1 decreased in all tested tissues, UCP-2 increased by 15% and 6 fold in muscle and white adipose tissue and UCP-3 increased 2.5 and 10 fold in muscle and epididymal adipose tissue, respectively. In female ASP-deficient mice UCP-1 decreased in all tissues, UCP-2 increased by 10% and 40% in inguinal and brown adipose tissue, respectively, and UCP-3 remained stable in all tissues. High fat diet nullified these differences, and decreased all wild-type UCP levels.
We propose that UCP-2 and 3 assume the role of UCP-1 in fuel utilization, thus helping mice face an increased energy load in the absence of ASP.
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Austin, Emily. "Homeostatic regulation of induced [beta]-cell mass expansion in mice." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101701.
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Current therapies do not prevent the devastating complications associated with type 1 and 2 diabetes. Novel therapies seek to restore a functional beta-cell mass through stimulating endogenous beta-cell mass expansion. Whilst there is considerable evidence that the beta-cell mass is under homeostatic regulation in the normal pancreas, it is unclear if such regulation exists in the context of induced beta-cell mass expansion. The aim of this study was to demonstrate that beta-cell mass expansion resulting from the induction of islet cell neogenesis is subject to long-term homeostatic control in the normoglycemic mouse adult pancreas.A pentadecapeptide fragment of Islet Neogenesis Associated Protein (INGAP 104-118) was administered daily to adult C57BL/6J mice for 12 weeks. Four animals from the INGAP104-118 treatment group and control group were sacrificed each week. The pancreas was removed from each mouse and stained for insulin. beta-cell mass was calculated as the organ weight multiplied by the percent of insulin+ area of total tissue area. Contrary to our expectations, there was no change in the total beta-cell mass in INGAP104-118-treated animals compared to control. Reanalysis of the stained tissue sections was preformed, and insulin+ structures were classified as being: (1) a duct islet, (2) a cluster of insulin+ cells, or (3) a mature islet. The density (#/mm2) of duct islets, clusters, and total structures in INGAP 104-118-treated animals was significantly increased; conversely, the density of mature islets was significantly decreased. The increase in cluster density suggests that INGAP104-118 induced neogenesis in the pancreas of treated animals. Poisson regression revealed 9th order polynomial time trends in the structure densities. Though these time trends differed between the classes of structures, they were identical in INGAP104-118 and control animals for each class of structure, suggesting an external stimulus was acting equally on both groups.
While this study did not determine if there is homeostatic regulation of induced beta-cell mass expansion, it did reveal important aspects for the design of a future study to address this issue. The definitions for structure classification must be well-established and rates of beta-cell replication should be determined.
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Staubs, Patricia A. "Oxygen Consumption and Carbon Dioxide Production in Prairie Deer mice (Peromyscus maniculatus bairdii) Kept in Various Group Densities and Reproductive Conditions." W&M ScholarWorks, 1992. https://scholarworks.wm.edu/etd/1539625727.
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Scott, Adrienne S. "BALBc mice develop pulmonary fibrosis after six months of cigarette smoke exposure." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98795.
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Rationale. Idiopathic pulmonary fibrosis in humans is associated with chronic cigarette smoking. At present only an acute model exists for lung fibrosis research. Objective. Describe a chronic animal model of lung fibrosis produced by cigarette smoke exposure. Methods. Six BALB/c mice have been exposed to two unfiltered cigarettes a day, 5 days a week for 6 months. Results. The phenotype was characterized by lung mechanics, histology and gene expression. Tissue elastance (compliance) and resistance was observed to be significantly elevated in the cigarette smoke-exposed mice compared to untreated controls. Histologically, airspace size in lungs of smoke exposed mice assessed by mean Linear Intercept and percent area of tissue was significantly decreased and increased respectively compared to controls. Inflammatory cell counting resulted in a significant increase in neutrophils in experimental mice. Assessment of Collagen type I clearly demonstrated a prominent interstitial deposition in smoke-exposed mice compared to controls. Conclusions. These data demonstrate that BALB/c mice are susceptible to the development of pulmonary fibrosis following chronic cigarette smoke exposure. This model could be an important contribution to the study of idiopathic pulmonary fibrosis in humans.
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Clark, Yvonne Yumiko. "Antioxidant Treatment of Muscle Wasting and Fatigue in Tumor-Bearing Mice." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1373844738.
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Johansson, Catarina. "Physiological changes in mice deficient in different subtypes of thyroid hormone receptors : a focus on studies of heart and muscle /." Stockholm, 1999. http://diss.kib.ki.se/1999/19990429joha/.
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Mehan, Ryan Scott. "The Role of Matrix Metalloproteinase-9 in Remodeling of Skeletal Muscle Connective Tissue in Mice." Thesis, University of Colorado at Boulder, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3562013.
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The basal lamina of skeletal muscle is a specialized region of extracellular matrix (ECM) comprised primarily of type IV collagen. Remodeling of the basal lamina, through altered expression or degradation of type IV collagen, is an important component of muscle plasticity. Matrix metalloproteinase-9 (MMP-9) is an inducibly expressed enzyme that degrades type IV collagen, and thus its enzymatic activity may play a key role in maintenance and plasticity of muscle structure and function. The purpose of this dissertation was to investigate the role of MMP-9-induced remodeling during normal development, exercise-induced injury, post-injury repair and aging of skeletal muscle.
Inactivation of the MMP-9 gene by homologous recombination resulted in decreases in muscle cross sectional area and enrichment of fast-twitch fiber types in several adult hindlimb muscles. Despite these compositional changes force production in MMP-9 null muscle remained normal.
Using a downhill running model of injury, I found that plasma concentration of MMP-9 in WT mice increased immediately exercise, while inactivation of the MMP-9 gene resulted in a significant decrease in post-injury muscle sarcolemmal damage. The source of MMP-9 appeared to be white blood cells and not muscle tissue itself, indicating the enzyme's activity might be required for immune cell infiltration of damaged muscle. However, using a chemically induced model of muscle injury, I found that immune cell infiltration was not diminished in MMP-9 null mice. Similarly, MMP-9 inactivation did not impair muscle stem cell activity or muscle regeneration. Thus while MMP-9 is involved in the magnitude of the injury response it appears to be dispensable for critical aspects of the post-injury repair process.
Finally, hindlimb muscles of older WT mice had increased type IV collagen content compared to younger mice, despite the two age groups having similar levels of COL4a1 mRNA expression. Older mice also exhibited reduced MMP-2, but not MMP-9, expression in muscle, and MMP-9 inactivation did not alter collagen levels in older mice. Thus, while aging is accompanied by altered basal lamina composition MMP-9 does not appear to play a critical role in this phenomenon.
In summary, these findings demonstrate that MMP-9 is involved in most, but not all, of the remodeling events studied, with aging being the exception.
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Alkahtani, Reem. "Changes in the Expression of Thin Filament-Associated Proteins in Colonic Smooth Muscle from Mice During Inflammation." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/220.
Full textAbstract:
The contractility of smooth muscle in inflammatory bowel disease and experimental colitis is reduced due to inhibition of neurotransmitter release and a decrease in the response of smooth muscle to contractile agonists. We and others have shown that inflammation induced by TNBS treatment alters the expression and/or activity of signaling molecules involved in the regulation of Ca2+ mobilization, MLC20 phosphorylation and contraction in colonic smooth muscle. Although, thin filament- associated proteins such as calponin, caldesmon, tropomyosin and smoothelin do not directly participate in contraction, they regulate acto-myosin interaction and thus, muscle contraction. Calponin, caldesmon and tropomyosin inhibit actomyosin interaction and the inhibition is relieved upon phosphorylation of these proteins. Recent studies have shown that visceral smooth muscle from smoothelin knockout mice exhibited decreased contraction. However, the effect of inflammation on the expression of thin filament- associated proteins is not known. The aim of the present study is to determine the changes in the expression of calponin, caldesmon, tropomyosin, and smoothelin in colonic circular smooth muscle from TNBS- and DSS-induced colitis in mice. The animals were euthanized on day 3 and a segment of inflamed distal colon was removed. Colonic muscle strips from colitis mice and control mice were dissected for western blot and real-time RT-PCR analysis; contraction was measured by scanning micrometry in cells isolated from the muscle strips. Contraction in response to acetylcholine in muscle cells isolated from colonic muscle strips derived from mice with TNBS colitis was significantly inhibited compared with the response of cells derived from untreated colon or colon treated with ethanol. Expression of α-actin, γ-actin calponin, caldesmon, smoothelin-A and tropomyosin mRNA in muscle strips from TNBS or DSS colitis was significantly increased compared to control animals. Similarly, expression of α-actin, calponin, caldesmon, smoothelin-A and tropomyosin protein as determined by western blot was significantly increased compared to control animals. We conclude that the expression of α-actin, γ -actin calponin, caldesmon, smoothelin-A and tropomyosin is upregulated in colonic circular smooth muscle from TNBS or DSS colitis. Increase in the expression of calponin, caldesmon and tropomyosin, which act to inhibit acto-myosin interaction, could contribute to decrease in smooth muscle contraction.
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Leroy, Brendan A. "Immunological characterization and localization of cell cycle regulatory proteins in preimplantation mouse embryos." Virtual Press, 1999. http://liblink.bsu.edu/uhtbin/catkey/1125138.
Full textAbstract:
The anticonvulsant drug, Dilantin, in many cases must be taken by epileptic mothers to control seizures during pregnancy, but unfortunately, it has been characterized as a human teratogen. It has also been demonstrated that many of the teratogenic effects of Dilantin occur during postimplantation, but some studies implicate a detrimental role for Dilantin during the preimplantation stages of development. Some of the postimplantation effects include congenital malformations and the potential'loss of the fetus. Our lab has proposed that in preimplantation mouse embryos the drug may be altering the timing of expression of cell cycle regulatory proteins and therefore, we have begun to examine the expression of these proteins. Thus, it was the goal of this study to characterize and localize various cell cycle proteins at specific time points in normal in vivo preimplantation mouse embryos, as this will provide important baseline information for studies on how anticonvulsant drugs may alter cell cycle regulation in embryos.Western blotting has confirmed the presence of cyclin BI in G1 of the first cell cycle. Both cyclin E and CDK2 were not detected in GI or G2/M of the first cell cycle or GI of the second cell cycle.From the immunogold TEM experiments, the density of cyclin B1 staining was observed to be the highest at G1 of the first cell cycle and declined at S and G2/M. Cyclin B 1 was detected in all regions of the embryo including the microvilli, cortical cytoplasm, interior cytoplasm, and was observed to be associated with vesicles and some filaments. The gold particles at GI, S, and G2/N4 of the first cell cycle and G1 of the second cell cycle appear to be associated with filamentous and membraneous structures and not free in the cytoplasmic spaces. Cyclin B 1 expression was more concentrated around vesicles at G1 of the first cell cycle and in general, was more concentrated around vesicles than in microvilli and cortical cytoplasm, interior cytoplasm, or around filaments at each cell cycle stage tested.Department of Biology
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Kaluarachchi, Thambilipitiyage Kusumsiri Priyantha Kumara. "Impact of collagen type X deficiency on bone fracture healing." Thesis, Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk/hkuto/record.jsp?B23501807.
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Lejmi, Mrad Rim. "Pathological and genetic analysis of host susceptibility to cardiovirulent coxsackievirus B3 infection in mice." Thesis, University of Ottawa (Canada), 2005. http://hdl.handle.net/10393/26953.
Full textAbstract:
Nearly fifty percent of North American myocarditis cases are associated to coxsackievirus group B, type 3 (CVB3) infection. CVB3 infection of mice provides a useful model to study pathogenic mechanism of myocarditis. The objective of this study is to test the hypothesis that susceptibility, during the acute CVB3 infection, is under polygenic control including H2 as well as the non H-2 genes.
To identify differential parameters of the disease, and if they are influenced by the H-2 haplotype, several phenotypic traits were characterized. Three inbred strains of mice and two congenic strains were infected with CVB3. Differences in survival, body weight loss, quantification of myocarditis and quantification of sarcolemmal disruption were found by comparing three sets of mice sharing the same H-2 haplotype but not the same background. It was determined that host susceptibility to CVB3-induced myocarditis is mainly controlled by "background" genes.
Moreover, because there is a naturally occurring variability among inbred mice, ten inbred strains of mice were used for the genetic analysis of four CVB3-induced phenotypes: survival, body weight loss, heart viral load and quantification of sarcolemmal disruption. It was concluded that the strains could be divided into three groups: the highly resistant, the resistant to intermediate strains and the highly susceptible strains. This phenotypic data on commonly used and genetically diverse inbred mouse strains sets up the platform for a detailed analysis of the genetic basis of susceptibility to CVB3.
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Scott, Ryan 1981. "Investigating the natural history of human islet-derived duct-like structures transplanted subcutaneously into nude mice." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112362.
Full textAbstract:
Islet plasticity has proven to be an important platform for the engineering of alternative islet tissue for transplantation. In vitro studies have shown the ability of islets to transdifferentiate into duct-like epithelial structures (DLS) thought to possess progenitor cells capable of replenishing damaged tissue within the pancreas. The aim of this study was to investigate the natural history of human derived duct-like epithelial structures transplanted into nude mice.Human islet derived duct-like structures from three cadaver pancreases were subcutaneously transplanted into 6-8 week old male HSD athymic nude-Foxn1 mice. Six mice were sacrificed at day 3, 7, 14 and 21 from each time period. DLS were also placed in matrigel for in-vitro control samples. DLS were processed for immunohistochemistry for endocrine markers, epithelial markers, cell death and proliferation markers, islet maturation markers and angiogenic factors.
Our results show that as DLS are transplanted, there is an increase in cell death and proliferation. This increase in cell death and proliferation causes an increase in PDX-1 expression as well as VEGF, an angiogenic factor. But over time, transplanted DLS do not show an increase in cell death and show a small decrease in cell proliferation from pre-transplanted DLS. At day 3 of engraftment, DLS show a significant expression of PDX-1. We see a small increase in endocrine tissue after 3 days of transplantation, then an increase in endocrine cell death, which returns the percentage of endocrine cells back to pre-transplantation levels at day 21. DLS were shown to express VEGF, and once transplanted into an initial hypoxic environment there is a substantial increase in expression, followed by a recruitment of microvessels. Although there is a dynamic change in expression of cell markers throughout engraftment, there is no significant change in DLS size, nuclei per DLS or cell morphology over time.
DLS have been shown to survive subcutaneous transplantation and possess an initial increase in cell proliferation leading to increases in PDX-1 and VEGF expression. Transplanted DLS have shown to possess significant angiogenic properties with the recruitment of microvessels into subcutaneous DLS grafts. Subcutaneous DLS transplantation could be used in combination with islet transplantation to alleviate current problems with islet transplantation such as islet cell death and insufficient blood supply.
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Wheeler, Elizabeth H. "Natural killer cell activity in mice bearing Lewis lung carcinoma." Virtual Press, 1985. http://liblink.bsu.edu/uhtbin/catkey/416656.
Full textAbstract:
Natural killer (NK) cells are important in limiting tumor dissemination. The NK activity in C57B1/6 mice bearing Lewis lung carcinoma (LLC) was monitored during tumor development. During the initial period of tumor growth, NK activity was enhanced. As tumor growth progressed, NK activity became suppressed. Depletion of macrophages from the spleen cells of tumor-bearing mice restored the NK cytotoxic response. Plasma prostaglandin E2 (PGE2) concentrations were measured by a radioimmunoassay and found to become elevated during the course of tumor growth. To determine whether the suppressed NK activity might have been a result of the elevated levels of PGE2, mice were treated with a prostaglandin synthesis inhibitor, indomethacin. Indomethacin treatment prevented the rise in plasma PGE2 concentrations and the suppression in NK activity. These results support the hypothesis that the suppression of NK activity in tumor bearers is mediated by PGE2 which might be produced by the host's suppressor macro-phages.
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Thayer, William R. "Part I characterization of MyoR in C2C12 mouse fibroblasts. Part II isolation and characterization of a novel class II bHLH transcription factor from the black widow spider, latrodectus hesperus." Scholarly Commons, 2004. https://scholarlycommons.pacific.edu/uop_etds/598.
Full textAbstract:
PART I
The basic helix-loop-helix (bHLH) family of transcription factors are involved in a variety of developmental processes. MyoR is the mouse homologue of the human transcription factor ABF-1 . MyoR is classified as a class II basic-helix-loop-helix transcription factor. In order to better understand the relationship between MyoR and muscle cell differentiation, we analyzed the temporal expression at both the mRNA and protein level. Unlike previous studies, we have utilized reverse transcriptase quantitative PCR to analyze mRNA expression. This allows quantitative analysis of MyoR mRNA levels during muscle cell differentiation. We have also analyzed MyoR expression at the protein level. Our studies suggest that the temporal expression of MyoR at the mRNA level is similar to the expression profile seen at the protein level. To ascertain differences in the MyoR DNA-binding activity during myogenesis we performed EMSA. Results suggest that changes in MyoR expression fail to account for differences in the DNAbinding complexes to an E-box site.
Part II
Members of the basic helix-loop-helix (bHLH) family are required for a number of different developmental pathways, including lymphopoiesis, myogenesis, neurogenesis and sex determination. Screening a eDNA library prepared from silk-producing glands of the black widow spider, we have identified a new bHLH transcription factor named BW6. Within the bHLH region, BW6 shows considerable conservation with other HLH proteins, including Drosophila melanogaster achaete and scute, as well as three HLH proteins identified by gene prediction programs. The expression pattern of bw6 is restricted to a subset of silk producing glands, which includes the tubuliform and major ampullate glands. BW6 is capable of binding an E-box element as a heterodimer with E2A, but was unable to bind this motif as a homodimer. BW6 is also capable of inhibiting the transactivation of rE47 in mammalian cells. BW6 represents the first example of a silk-gland-restricted bHLH protein, and its expression pattern suggests that BW6 may play a role in regulating differentiation of cells in the spider that control silk gland formation or egg case silk gene expression.