Dissertations / Theses: 'Mutant Phenotype'

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Sofia, Francesca. "Emx1 null mutant mouse phenotype : potential implications for human epilepsy." Thesis, Open University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251365.

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Rejeski, Kai Dannebom [Verfasser], and Michael [Akademischer Betreuer] Lübbert. "Elucidation of a hypersplicing phenotype in SRSF2 mutant myeloid malignancy." Freiburg : Universität, 2021. http://d-nb.info/1236500849/34.

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Morrison, Gillian M. "Analysis of the pulmonary inflammatory phenotype of the CF mutant mouse." Thesis, University of Edinburgh, 1999. http://hdl.handle.net/1842/22507.

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Studies using isolated alveolar macrophages, led to the hypothesis that the pulmonary inflammatory cells of the Cftr^tm1HGUmouse function normally when given a direct inflammatory stimulus and that another aspect of the host defence system is not functioning adequately to deal with repeated exposure to low level non-specific bacteria. Recent studies on the human airway defensin molecule, hBD-1, reveal that its bactericidal properties are inactivated by high salt concentrations. It is possible that the airway surface fluid of CF patients has a raised NaCl concentration and relates to a defective host defence system caused by the CFTR mutation. This thesis describes the identification and characterisation of a mouse β-defensin gene, Defb1, sometimes referred to as mBD-1, which was shown to be homologous to the human airway beta defensin hBD-1. It was found that Defb1 was expressed in a variety of tissues including the airways and like hBD-1 is not upregulated by LPS. A genomic targeting vector was constructed and Defb1 successfully knocked out in the mouse. This study also led to the isolation of a 150kb BAC contig which was shown to contain members of both the alpha and beta defensin gene families. Using low stringency hybridisation a novel murine beta defensin gene was identified which is not highly expressed in the airways under normal conditions although it appears to be weakly upregulated by LPS. A second human beta defensin gene, hBD-2, was recently identified which was shown to be upregulated in the airways by inflammatory stimuli, thus this novel murine gene is similar to hBD-2 both in structure and function. It is hoped that the study of the murine beta defensin gene family will lead to a clearer understanding of the normal function of defensins as well as of the consequences of their dysfunction in CF.

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Benn, Caroline Louise. "Targeting mutant huntingtin to the nucleus accelerates phenotype onset in transgenic mice." Thesis, King's College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401268.

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Donzelli, A. "BEHAVIOURAL PHENOTYPE AND ELECTROENCEPHALOGRAPHIC PROFILE OF ADOLESCENT AND ADULT SNAP-25+/- MUTANT MICE." Doctoral thesis, Università degli Studi di Milano, 2013. http://hdl.handle.net/2434/214980.

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Synaptosomal-associated protein of 25 kDa (SNAP-25) is a protein that participates in the regulation of synaptic vesicle exocytosis through the formation of the soluble N-ethylmaleimide-sensitive proteine (NSF) attachment protein receptor complex and modulates voltage-gated calcium channels activity. Snap25 gene has been associated with schizophrenia, and bipolar disorder, and lower levels of SNAP-25 have been described in patients with schizophrenia. In particular several SNAP-25 intronic single polymorphisms were linked to attention deﬁcit hyperactivity disorder, one of the most common neuropsychiatric diseases among children and adolescents. The most animal models of this pathology, available until now, are characterized by reduced SNAP-25 level in the CNS: the coloboma mice, and the spontaneously hypertensive rats (SHR). However none of them can completely ricapitulate all the core features of the human patology. Thus we used adult SNAP-25 heterozygous (SNAP-25+/−) mice in comparison with age-matched wild type mice (SNAP-25+/+) to investigate at which extent the reduction of the protein levels affects neuronal network function and mouse behavior, and the possible therapeutic effect of antiepileptic drugs. We also characterized adolescent SNAP-25+/- mice (6-7 weeks) in order to evaluate if they can be considered a new ADHD animal model. Firstly we analysed general health, sensory and motor abilities, and emotional behaviour in our animals, without finding any abnormalities in heterozygous mice. Since altered SNAP-25 level were associated with cognitive deficit, we performed T-maze test for the evaluation of spatial memory, latent inhibition test for attention, conditioned taste aversion and object recognition for associative memory. SNAP-25+/- resulted impaired in associative but not in spatial memory, probably because of the heterogeneous protein expression levels in different hippocampal areas, being more expressed in CA3, known to play a key role in associative memory, than in CA1, critical for long-term spatial memory. SNAP-25+/- has been associated to disease characterized by altered social behaviour, such as schizophrenia and bipolar disorder. We tested SNAP-25 mutant mice in sociability and social novelty test. Heterozygous showed impairment both in sociability and in social recognition. Pathologies characterized by SNAP-25 alterations show signiﬁcantly higher incidence of epilepsy. For this reason we recorded the cortical electric activity of mice and we found that SNAP-25 levels reduction was associated with network hyperexcitability, in terms of spike activity, which did not lead to spontaneous epileptiform behaviour. Acute treatment with antiepileptic drugs and Ca2+ antagonist normalized cerebral activity. Among these drugs, sodium valproate was more effective in blocking EEG and behavioural deficits. Since it is known the correlation between EEG alteration and cognitive deficits we can hypothesize that the mnemonic and social deficit are due to the abnormal EEG profile. Adolescents SNAP-25+/- mice showed the same deficits found in the adults. They also were hyperactivite, and were not susceptible to d-amphetamine treatment. These results are in line with the characteristic phenotype of ADHD children, that display cognitive deficits, problems in socialization and hyperactivity, normalized by stimulants. Recently EEG analysis was used as diagnostic tool to discriminate ADHD from other neuropsychiatric diseases. EEG in ADHD children is characterized by spikes and alteration in spectral power bands frequency. Spectral analysis heterozygous mice EEG recordings was caharacterized by spikes, a decrease in fast waves and a parallel increase in slow waves, as occur in ADHD children. Repeated exposition to a VLP solution (0.1%) reduced all the behavioural deficit and was effective in blocking spike activity for two weeks, when discontinued. SNAP-25+/- mice seem to be a promising ADHD animal model, able to recapitulate almost all the core symptoms of the human disease. Repeated treatment with VLP resulted effective in all the tests carried out in adolescents mice, in line with recent findings of its therapeutic effects on ADHD symptoms in x-fragile syndrome.

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Jolivet, Katell. "Cloning and characterisation of LDW1, an Arabidopsis thaliana mutant displaying a lesion-mimic, dwarf phenotype." Thesis, Imperial College London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.405621.

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Skowrońska, Anna Maria. "ATM mutant cellular phenotype in B-cell chronic lymphocytic leukaemia : clinical consequences and therapeutic implications." Thesis, University of Birmingham, 2013. http://etheses.bham.ac.uk//id/eprint/4720/.

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ATM germ-line mutations have been identified in a proportion of patients with chronic lymphocytic leukaemia (CLL) but their role in the development of this tumour remains unknown. In the course of this study it was established that ATM pathogenic mutations were increased among patients with chromosome 11q deletion/loss of one ATM allele when compared to healthy control individuals but not in those who did not acquire this deletion in their leukemic clone. The results indicate that ATM germ-line heterozygosity does not play a role in CLL but may influence disease progression through complete ATM loss and clonal expansion. The analysis of the clinical outcome among CLL patients from phase III LRF UK CLL4 trial identified a distinctive subgroup with a particularly poor prognosis. Those patients had bi-allelic inactivation of ATM gene and showed significantly reduced progression-free survival (PFS) compared to those with ATM wild-type or mono-allelic ATM defects. Furthermore, they had equally poor PFS as those with mono- and bi-allelic TP53 abnormalities. The clinical implication of this finding might include re-consideration of the treatment strategies for this particular subgroup of patients. The improved understanding of the biological background of progressive and resistant CLL tumours, such as those with TP53 or ATM defects, results in a development of further targeted treatment strategies. The assessment of their efficacy and toxicity could be facilitated by CLL xenograft models. The optimization strategies overcoming the limitations of existing xenograft model were investigated during the course of this study. The results showed that partial depletion of patient CD3+, CD4+ or CD25+ cells prior to injection into NOG mice can prolong the engraftment of CLL cells within xenogenic microenvironment hence, providing expanded period of time for testing new therapeutic agents.

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Bukowski-Wills, Jimi-Carlo. "Molecular links between genotype and phenotype in the albino-Swiss PKC-gamma mutant (AS/AGU) rat." Thesis, University of Glasgow, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.443440.

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Plong, Alexander. "Developmental and leaf senescence phenotype analysis in Arabidopsis thaliana| The atx4 (AT4G27910) mutant displays delayed leaf senescence and the kdm5b_1 (AT5G46910) mutant has larger seeds." Thesis, California State University, Long Beach, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=1603973.

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Leaf senescence is the final stage of leaf development that results in the highly ordered degeneration of cellular organelles and reallocation of nutrients to younger developing tissue. These cellular changes are accompanied by global changes in gene expression. Epigenetic modifications, such as DNA methylation, changes in histone variants, and covalent modification of histones have been shown to influence the expression of genes. Previous ChIP-seq and RNA-seq analyses revealed a correlation between the trimethylation of histone H3 lysine 4 (H3K4me3), a mark associated with active transcription, and the expression of a subset of senescence associated genes (SAGs) during leaf senescence in Arabidopsis thaliana. In this study, T-DNA insertion mutants of five histone methyltransferases (HMTases or ATX/ATXR) and five histone demethylases (HDMases or KDM5b) were examined to determine whether the expression of targeted SAGs was affected. In addition, total chlorophyll and protein levels, as well as plant development were investigated to determine whether these mutants function in regulating plant development and catabolism during senescence. The results show that while the expression of target SAGs were not affected by the mutants, other processes were affected. atx4 was observed to have higher levels of chlorophyll and protein, which indicates ATX4 may function in positively regulating catabolism during leaf senescence. Additionally, kdm5b_1 was observed to have larger seeds, which indicates KDM5b_1 may function to restrict seed size in Arabidopsis.

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Li, Xiaona. "Mass spectrometry-based metabolomics study on KRAS-mutant colorectal cancer and rheumatoid arthritis." HKBU Institutional Repository, 2018. https://repository.hkbu.edu.hk/etd_oa/540.

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Ample studies have shown that perturbation of metabolic phenotype is correlated with gene mutation and pathogenesis of colorectal cancer (CRC) and rheumatoid arthritis (RA). Mass spectrometry (MS)-based metabolomics as a powerful and stable approach is widely applied to bridge the gap from genotype/metabolites to phenotype. In CRC suffers, KRAS mutation accounts for 35%-45%. In previous study, SLC25A22 that encodes the mitochondrial glutamate transporter was found to be overexpressed in CRC tumor and thus to be essential for the proliferation of CRC cells harboring KRAS mutations. However, the role of SLC25A22 on metabolic regulation in KRAS-mutant CRC cells has not been comprehensively characterized. We performed non-targeted metabolomics, targeted metabolomics and isotope kinetic analysis of KRAS-mutant DLD1 cells with or without SLC25A22 knockdown using ultra-high performance liquid chromatography (UHPLC) coupled to Orbitrap MS and tandem MS (MS/MS). In global metabolomics analysis, 35 differentially regulated metabolites were identified, which were primarily involved in alanine, aspartate and glutamate metabolism, urea cycle and polyamine metabolism. Then targeted metabolomics analysis on intracellular metabolites, including tricarboxylic acid (TCA) cycle intermediates, amino acids and polyamines, was established by using LC-MS/MS coupled with an Amide BEH column. Targeted metabolomics analysis revealed that most TCA cycle intermediates, aspartate (Asp)-derived asparagine, alanine and ornithine (Orn)-derived polyamines were strongly down-regulated in SLC25A22 knockdown cells. Moreover, the targeted kinetic isotope analysis using [U-13C5]-glutamine as isotope tracer showed that most of the 13C-labeled TCA cycle intermediates were down-regulated in SLC25A22-silencing cells. Orn-derived polyamines were significantly decreased in SLC25A22 knockdown cells and culture medium. Meanwhile, accumulation of Asp in knockdown of GOT1 cells indicated that oxaloacetate (OAA) was majorly converted from Asp through GOT1. Exogenous addition of polyamines could significantly promote cell proliferation in DLD1 cells, highlighting their potential role as oncogenic metabolites that function downstream of SLC25A22-mediated glutamine metabolism. SLC25A22 acts as an essential metabolic regulator during CRC progression as promotes the synthesis of TCA cycle intermediates, Asp-derived amino acids and polyamines in KRAS-mutant CRC cells. Moreover, OAA and polyamine could promote KRAS-mutant CRC cell growth and survival. Rheumatoid arthritis (RA) is a chronic, inflammatory and symmetric autoimmune disease and a major cause of disability. However, there is insufficient pathological evidence in term of metabolic signatures of rheumatoid arthritis, especially the metabolic perturbation associated with gut microbiota (GM). Based on consistent criteria without special diet and therapeutic intervention to GM, we enrolled 50 RA patients and 50 healthy controls. On basis of the platform of UHPLC-MS and GC-MS, were performed for the non-targeted metabolomics to investigate alterations of endogenous metabolites in response to RA inflammation and interaction with GM. 32 and 34 significantly changed metabolites were identified in urine and serum of patients with RA, respectively. The altered metabolites were identified by HMDB, METLIN database or authentic standards, and mostly metabolites were attributed into tryptophan and phenylalanine metabolism, valine, leucine and isoleucine biosynthesis, aminoacyl-tRNA biosynthesis and citrate cycle. To obtain alterations of more components in tryptophan and phenylalanine metabolism, we developed and validated a targeted metabolomics method of 19 metabolites by using LC-QqQ MS. Combining the results of targeted metabolomics with global metabolomics, significantly up-regulated kynurenine (KYN), anthranilic acid (AA) and 5-hydroxylindoleacetic acid (HIAA) simultaneously in urine and serum was found to implicate the activation of tryptophan metabolism under the condition of RA, which acted pro-inflammatory roles in inflammation and was closely correlated with GM. IDO/TDO functioned as a pro-inflammation mediator was overexpressed in RA patients. Urinary kynurenic acid and serum serotonin that have impacts on anti-inflammation in immune system were down-regulated in RA patients. The levels of phenylacetic acid and phenyllactic acid serving as a pro-inflammatory and an anti-inflammatory agent, respectively, increased in serum of patients with RA. Moreover, certain essential amino acids (EAAs), and mostly conditional EAAs were decreased in RA patients, which have been reported to inhibit cell proliferation of immune cells. In particular, deficiency of branched chain amino acids (BCAAs, valine and isoleucine) was observed in serum of patients with RA, which may lead to muscle loss and cartilage damage. The specificity of all altered metabolites resulted from RA was considerably contributed through the GM-derived metabolites. The findings revealed that GM-modulated RA inflammation was mainly resulted from tryptophan and phenylalanine metabolism, and amino acid biosynthesis, which may provide more information for better understanding the RA mechanism.

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Bégot, Laurent. "Caractérisation du mutant dal1-2 d'Arabidopsis thaliana, affecté dans le développement précoce du chloroplaste." Université Joseph Fourier (Grenoble ; 1971-2015), 1999. http://www.theses.fr/1999GRE10054.

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Le mutant d'arabidopsis thaliana dal1-2, etiquete par un element transposable ac, est bloque precocement dans le developpement du chloroplaste. Son etude phenotypique a permit de mettre en evidence une couleur des feuilles variant du jaune au vert clair, au cours de son developpement. Morphologiquement, des coupes histologiques de feuilles montrent une desorganisation de la couche palissadique mesophyllienne. Le nombre de chloroplastes par cellule est plus important chez le mutant compare avec le sauvage mais leur taille est plus petite. La structure des chloroplastes par microscopie electronique a transmission montre une desorganisation et une quantite reduite des membranes thylacoidiennes. Les dosages realises sur les chlorophylles, carotenoides et lipides indiquent une forte reduction quantitative de ces molecules chez le mutant. La respiration chez le mutant est normale mais la photosynthese est residuelle pour un stade de developpement avance du mutant. Dal1-2 n'est pas affecte dans la skotomorphogenese. Au niveau genetique, l'isolement de l'adnc et du gene ont ete realises. L'expression du gene dal est absente chez le mutant. Une seule copie du gene dal est presente dans le genome nucleaire d'arabidopsis thaliana et celui-ci appartient a une famille de genes. L'expression de dal est elevee dans les boutons floraux et les fleurs. La proteine dal contient une sequence d'adressage chloroplastique et est importee dans le chloroplaste. L'analyse de l'expression de genes impliques dans le developpement des organites a permit de montrer clairement que la coordination de l'expression de genes nucleaires et chloroplastiques est toujours assuree chez le mutant dal1-2. L'expression des genes nucleaires de proteines ribosomiques est inchangee dans le mutant alors que l'expression des genes photosynthetiques cab et rbcs est reduite. Globalement, l'expression des genes mitochondriaux montre un niveau d'expression normal. Par contre, l'expression de tous les genes chloroplastiques testes est fortement reduite. L'analyse de l'expression de l'adnr 16s chloroplastique revele la presence de 50% d'arnr 16s non matures. Une explication possible etant que la proteine dal soit impliquee dans la maturation post-transcriptionnelle des arnr 16s. Ainsi, l'absence de la proteine dal conduirait a une chute de l'assemblage des ribosomes 70s, et par consequent a une perte de l'integrite chloroplastique.

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Коваль, Вікторія Миколаївна. "Генетичний поліморфізм шиншил." Магістерська робота, ЗНУ, 2020. https://dspace.znu.edu.ua/jspui/handle/12345/1394.

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Коваль В. М. Генетичний поліморфізм шин шил : кваліфікаційна робота магістра спеціальності 091 "Біологія" освітньої програми "Генетика" / наук. керівник О. М. Войтович. Запоріжжя : ЗНУ, 2020. 82 с.
UA : Робота викладена на 82 сторінках друкованого тексту, містить 14 таблиць та 12 рисунків. Перелік посилань включає 52 джерела. Об’єктом дослідження була приватна колекція шиншил. Мета роботи – оцінити генетичний потенціал приватної колекції шиншил за рівнем поліморфізму забарвлення. Методи дослідження – аналіз наукової літератури, гібридологічний аналіз та генетичне прогнозування. Складений та систематизований визначник алелів забарвлення шиншили. Проведено генетичний опис приватної колекції шиншил та складено генетич-ний портрет 15 тварин. Визначено особливо генетично цінні форми –гомозиготний бежевий, сапфір та гомобежевий фіолет. Підтверджено генетичну чистоту форм колекції та визначено перспективні напрямки проведення гібри-дизації з метою розкриття та реалізації генетичного потенціалу. Проаналізовано роботу генетичного калькулятора для розрахунку можливих забарвлень шин-шил, підтверджено його зручність як інструменту для зручного та швидкого моделювання можливих варіантів забарвлення за умови знання генотипів бать-ків. Отримані результати можуть бути використані як посібник для ефектив-ної роботи з штучними популяціями шиншил.
EN : The work is presented at 82 pages of printed text, containing 14 tables and 12 figures. The list of references includes 52 sources. The object of the study was a private collection of chinchillas. The purpose of this work was to evaluate the genetic potential of a private chinchilla collection by the level of color polymorphism. Research methods – scientific literature analysis, hybridological analysis and genetic prediction. The determinant of the chinchilla color alleles was compiled and organized. A genetic description of a private collection of chinchillas was conducted and a genetic portrait of 15 animals was completed. Particularly genetically valuable forms have been identified – homozygous beige, sapphire, and homobeige violet. The genetic purity of collection forms has been confirmed and promised directions for hybridization to identify and realize the genetic potential. The work of the genetic calculator for calculating the possible color of chinchillas is analyzed, and its convenience as a tool for the convenient and fast modeling of possible color variants, provided the knowledge of the parents' genotypes is confirmed. The obtained results can be used as a guide for effective work with artificial chinchilla populations.

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Bennett, William R. "Characterisation of two developmentally important genes mutated by transgene insertion in the laboratory mouse." Thesis, University of Bath, 1999. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301968.

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Charles, Tysheena Perkins. "Unraveling the phenotype of colicin cytoplasmic import (cim) mutants." [College Station, Tex. : Texas A&M University, 2008. http://hdl.handle.net/1969.1/ETD-TAMU-2321.

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Alaynick, William Arthur. "Phenotypic characterization of estrogen-related receptor gamma mutant mice." Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2006. http://wwwlib.umi.com/cr/ucsd/fullcit?p3235013.

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Thesis (Ph. D.)--University of California, San Diego, 2006.
Title from first page of PDF file (viewed December 6, 2006). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.

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RANERI, MATTEO. "PLEIOTROPIC PHENOTYPE OF PSEUDOMONAS AERUGINOSA MUTANTS DEFECTIVE IN GLUCOSE UPTAKE." Doctoral thesis, Università degli Studi di Milano, 2019. http://hdl.handle.net/2434/618277.

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Pseudomonas aeruginosa è un patogeno opportunista che provoca una vasta gamma di infezioni nell’uomo. È noto che l’incidenza delle infezioni da P. aeruginosa è maggiore in persone che presentano elevati livelli di glucosio nel sangue, a causa della capacità del batterio di utilizzare il glucosio in eccesso come nutriente per la crescita. Pertanto, bloccare l’attività di proteine coinvolte nel trasporto o nell’utilizzazione del glucosio da parte del batterio potrebbe essere una buona strategia per lo sviluppo di farmaci anti-pseudomonas. Per valutare questa ipotesi, abbiamo costruito una serie di mutanti singoli e multipli difettivi nel trasporto del glucosio nel ceppo PAO1 di P. aeruginosa e li abbiamo analizzati per fenotipi correlati alla virulenza in saggi in vitro e in vivo, in due differenti modelli di infezione. In particolare, sono stati deleti i geni codificanti per i trasportatori della membrana interna Glt, GntP e Kgut, che mediano l’ingresso del glucosio e dei suoi derivati ossidati gluconato e 2-ketogluconato. Un triplo mutante privo dei suddetti trasportatori si è rivelato incapace di crescere su glucosio come unica fonte di carbonio (mutante GUN, Glucose Uptake Null). Più di 500 geni, che controllano sia funzioni metaboliche che la virulenza, sono espressi in modo differenziale nel mutante GUN rispetto al ceppo parentale. Coerentemente con i dati dell’analisi trascrittomica, i saggi di virulenza in vitro hanno mostrato che il mutante GUN si comporta diversamente dal ceppo parentale, avendo una ridotta capacità di formare biofilm e una maggiore secrezione di proteasi, piocianina e pioverdina. Inoltre, questo mutante ha una produzione alterata delle molecole segnale che attivano il sistema del quorum sensing. È interessante notare che il profilo trascrizionale e la maggior parte dei tratti fenotipici analizzati differiscono tra il mutante GUN e il ceppo parentale indipendentemente dalla presenza del glucosio, suggerendo che uno (o più) dei trasportatori deleti abbia una funzione addizionale non correlata al trasporto del glucosio. Infine, alcuni mutanti hanno mostrato un diverso grado di virulenza in saggi di infezione negli ospiti modello Caenorhabditis elegans e Galleria mellonella. In particolare, mentre in C. elegans la virulenza dei mutanti è risultata simile a quella del ceppo parentale PAO1, i mutanti deleti del gene kguT, che codifica per il trasportatore del 2-ketogluconato, sono meno virulenti di PAO1 in G. mellonella. L’attenuazione è particolarmente significativa per il doppio mutante ΔgntP ΔkguT e per il mutante GUN. Questo risultato suggerisce che l’efficacia antibatterica di composti che bloccano l’utilizzo del glucosio da parte di P. aeruginosa potrebbe presumibilmente variare a seconda della capacità del patogeno di adattarsi allo specifico contesto nutrizionale dell’ospite infettato. Una maggiore conoscenza delle interazioni metaboliche che avvengono tra patogeno ed ospite nel sito d’infezione diventa quindi sempre più necessaria per poter sviluppare terapie antibatteriche efficaci.
Pseudomonas aeruginosa is an opportunistic pathogen causing a wide range of infections in humans. Pathologies leading to hyperglycaemia have been associated with augmented risk of developing serious P. aeruginosa infections due to the ability of the bacterium to utilize glucose as carbon source for the growth. Therefore, preventing the import of glucose might be a good strategy to develop anti-pseudomonas drugs. To address this hypothesis, a collection of single and multiple glucose uptake defective mutants was generated in P. aeruginosa PAO1 and tested for virulence-related phenotypes in in vitro assays and in vivo, in two different infection models. In particular, we engineered mutants in genes encoding inner membrane (IM) proteins involved in the internalization of glucose and its oxidized derivatives gluconate and 2-ketogluconate, i.e. the Glt, GntP and KguT transporters. A triple mutant lacking these transporters was demonstrated to be completely unable to grow on glucose as sole carbon source (Glucose Uptake Null mutant, GUN). The transcriptomic analysis revealed a strong divergence in the GUN transcriptional profile relative to the parental strain, with more than 500 differentially expressed genes, controlling both metabolic functions and virulence traits. Consistent with the transcriptomic data, the GUN mutant showed a pleiotropic phenotype in the in vitro assays, with a reduction in biofilm formation and an increased secretion of proteases, pyocyanin and pyoverdine. Furthermore, the production of quorum sensing signal molecules was altered in this mutant. Interestingly, the gene expression profile and most phenotypic traits differ between GUN and the parental strain irrespective of the presence of glucose, suggesting a possible additional role for the deleted transporter(s). Finally, the in vivo assays demonstrated that while the virulence of all mutants in the Caenorhabditis elegans infection model was essentially comparable to that of the wild type strain, all mutants lacking kguT (i.e. the 2-ketogluconate transporter gene) and especially the double ΔgntP ΔkguT and GUN mutants, were attenuated in the Galleria mellonella model. This suggests that targeting glucose metabolism with specific drugs may alter P. aeruginosa pathogenicity depending on the ability of this pathogen to adapt to the specific nutritional context encountered at the site of infection. Therefore, a deeper knowledge of host-pathogen metabolic transactions is pivotal to develop effective antibacterial strategies based on hampering bacterial metabolic functions.

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Zhao, Yuming. "Phenotypic analysis of osteoclast lineage in c-fos mutant mice." Thesis, King's College London (University of London), 2003. https://kclpure.kcl.ac.uk/portal/en/theses/phenotypic-analysis-of-osteoclast-lineage-in-cfos-mutant-mice(fafcec7f-6480-4f8c-87b6-3cca60a475fb).html.

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Webster, Margaret Ann. "Floral morphogenesis in Primula : inheritance of mutant phenotypes, heteromorphy, and linkage analysis." Thesis, University of Leeds, 2005. http://etheses.whiterose.ac.uk/11275/.

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Interest in Primula flowers from both a horticultural and scientific perspective dates back over 400 years. Floral mutations were first used for ornamental value in the latter part of the 16th Century but had attracted little scientific attention. The phenomenon of floral heteromorphy as a mechanism to promote out-breeding was immortalised by the work of Darwin in the mid 19th Century. Subsequent analysis of this breeding system has attracted much attention, including the genetic definition of the S locus as a cluster of tightly linked genes that control pin and thrum flower development and mediate self-incompatibility. Mutant phenotypes of British Primula have been collected by the author for over twenty years. Classical genetic analysis of some of these mutants is included and provides the first detailed analysis of existing and new mutant phenotypes. Genetic analysis of these mutants is presented in the context of the ABC model of flower development. Detailed analysis of the early ontogeny of wild type and mutant flowers by scanning electron microscopy provides new insights into the control of Primula flower development. As Primula flowers were found to be homomorphic during early ontogeny development of pin and thrum heteromorphic features of Primula were investigated to maturity. A new heteromorphic feature was discovered; thrum flowers have a wider corolla tube mouth than pin flowers due to the corolla tube cells above the anthers being wider in thrum flowers than in pin flowers. Three of the mutant phenotypes Hose in Hose, Staminoid Carpels and sepaloid are predicted to arise through misexpression of a B function gene. The first two are dominant mutant phenotypes and all are linked to the S locus. A fourth recently discovered dominant mutant phenotype, Oakleaf, affects both leaf and flower development, and is also linked to 1he S locus. As 1he dominant nature of the Hose in Hose mutation precludes complementation tests three point crosses were used both as segregation tests and for mapping genes linked to the Primula S locus. Gene order was found to be Oak Leaf, S locus, Hose in Hose, with sepaloid either allelic to Hose in Hose or very tightly linked. In combination, these analyses have enabled 1he assembly of the first genetic map of genes around the S locus including flanking markers on either side.

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19

Roth, Ronelle. "Phenotypic characterization of maize bundle sheath defective mutants." Thesis, University of Oxford, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.339349.

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20

Frostell-Birge, Malin, and Mia Skocic. "Phenotypic Characterization of hns mutants of Aggregatibacter actinomycetemcomitans." Thesis, Umeå universitet, Tandläkarutbildning, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-97867.

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Aggregatibacter actinomycetemcomitans is associated with aggressive forms of periodontitis. The mechanisms that control the expression of virulence factors are essentially unknown. Histone-like nucleoid structuring protein, H-NS, is a DNA binding protein that has been shown to influence hundreds of genes in Gram-negative bacteria. H-NS usually acts as a transcriptional silencer and has a negative influence on gene expression. H-NS has not been studied in A. actinomycetemcomitans before, and its effects on gene expression in this species were lacking. This study aimed to investigate if lack of H-NS expression might result in apparent phenotypical differences regarding gene expression with emphasis on virulence. For this we have used the A. actinomycetemcomitans rough-colony serotype a strain, D7S, its smooth-colony derivative D7SS, and hns mutants of D7S and D7SS. Our results show that smooth colony strain D7SS releases a larger amount of vesicles as compared to the rough D7S. The D7S hns mutant appeared to exhibit pili that were shorter than those of the parental strain, and this was not due to altered expression of RcpA in the hns mutant. As judged by Silver-staining, and Western blot analysis, H-NS may influence the level of several proteins. Taken together, our study supports that H-NS is involved in the regulation of virulence factor expression in A. actinomycetemcomitans.

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Gautam, Deepshila, Imdadul Haq, and Aruna Kilaru. "Phenotypic Characterization of FAAH Mutants in Physcomitrella Patens." Digital Commons @ East Tennessee State University, 2020. https://dc.etsu.edu/etsu-works/7733.

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22

Guatam, Deepshila, Imdadul Haq, and Aruna Kilaru. "Phenotypic Characterization of FAAH Mutants in Physcomitrella Patens." Digital Commons @ East Tennessee State University, 2020. https://dc.etsu.edu/etsu-works/7734.

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23

Wong, Kung-yen Corinne, and 黃共欣. "Analysis of abnormal phenotypes of Hoxb3 mouse mutants generated by gene targeting." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B29158904.

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24

Dean, Deyrick Osmond. "Isolation and phenotypic characterisation of deletion mutants of dnaK." Thesis, University of East Anglia, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292657.

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25

Kennedy, Daniel Edward II. "Phenotypic Characterization and Gene Expression Analyses of a Penicillium marneffei Septin Mutant." Youngstown State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1340653587.

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26

Robins, Tiina. "Functional and structural studies on CYP21 mutants in congenital adrenal hyperplasia /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-529-1/.

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27

Weaver, Jun Eon. "Characterizing phenotypes of Pichia pastoris mutants that show enhanced secretion of recombinant proteins." Scholarly Commons, 2014. https://scholarlycommons.pacific.edu/uop_etds/188.

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In effort to understand and isolate genes that are associated with protein secretion, the Lin-Cereghino laboratory at University of the Pacific created mutant strains of Pichia pastoris using the restriction enzyme mediated integration method. The mutants exhibited an unusual ability to supersecrete beta-galactosidase, due to the effects of a randomly disrupted gene by pREMI-Z. To learn more about the novel effects of the gene disruption, nine beta-galactosidase supersecreters ( bgs ) have been characterized for their phenotypes such as growth rate, cell wall integrity, and ability to produce and secrete various types of recombinant proteins. The mutants showed various population doubling times, which ranged from 1.7 to 2.4 hours. Generally, the mutants with severely diminished growth rates had much lower secretion of the reporter proteins. The mutants also showed different levels of cell wall (osmotic) defect, indicated by moderate to severe leakage of alkaline phosphatase from the vacuole. It was revealed that the cell wall defect was not necessarily associated with increased protein secretion, which suggests that the cell wall may not be a limiting barrier for the secretion of most reporter proteins. The result of the reporter study suggests that the secretion phenotypes of bgs mutants were protein specific and likely to be dependent upon the structure of the secreted protein rather than the size.

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28

Kryzskaya, Darya. "Genetic interactions between suppressors of the slow defecation of phenotype of clk-1 mutants." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106585.

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Many genes that are involved in nutrient and energy utilization and storage are conserved between humans and C. elegans. One of the genes involved in worm mitochondrial respiration is clk-1. This gene encodes an enzyme required for ubiquinone biosynthesis. One of the phenotypes of clk-1 mutants is altered defecation cycle: the slowing down of the defecation cycle and the inability to defecate faster at higher temperatures. these phenotypes are independent of one another. Several lines of evidence suggest that the slowed defecation of clk-1 mutants is due to alterations in lipoprotein/cholesterol metabolism because the mutant phenotype can be suppressed by the reduction of dietary cholesterol, administration of drugs affecting lipoprotein metabolism, and mutating genes involved in lipoprotein metabolism. These mutations can be separated into two classes: those which suppress the clk-1 slow defecation at 20 as well as after the shift to 25°C (class I) and those which only suppress it at 20°C (class II). Worm dsc-4 (lipoprotein assembly) and dsc-3 (metabolism of bile-like molecules) are class I suppressors. Both of these mutations restore the ability of clk-1 mutants to react to the temperature shifts. In this study we identified a novel class I suppressor pgp-2 and classified sod-4 as a class II suppressor. pgp-2 encodes a protein essential for the biosynthesis of the worm intestinal lysosome-related organelles. Mutations in both pgp-2 and sod-4 are unable to restore the ability of clk-1 worms to react to the temperature shifts. Combining different class I mutants as well as combining class I with class II mutant sod-4 revealed that the genetic interactions between class I mutants as well as genetic interactions between class I and class II mutants are hard to predict.
Plusieurs des gènes impliqués dans l'utilisation des nutriments et de l'énergie ainsi que pour leur stockage sont conservés de l'humain à C. elegans. Un des gènes impliqué dans la respiration mitochondriale du nématode est clk-1. Ce gène encode pour une enzyme requise à la synthèse d'ubiquinone. Un des phénotypes des mutants clk-1 est une altération du cycle de défécation. Chez ces mutants, le cycle de défécation est ralenti et celui-ci ne s'accélère pas à des températures plus élevées, comme observé chez le nématode sauvage. Ces phénotypes sont indépendants l'un de l'autre. Plusieurs résultats expérimentaux suggèrent que le ralentissement du cycle de défécation chez les mutants clk-1 est du à des altérations du métabolisme lipoprotéines/cholestérol car ce phénotype peut être supprimé par la réduction du cholestérol provenant de la diète, par l'administration de composés affectant le métabolisme des lipoprotéines et par mutation des gènes impliqués dans le métabolisme des lipoprotéines. Ces mutations peuvent êtres divisées en 2 classes : celles qui suppriment le ralentissement du cycle de défécation à 20oC aussi bien qu'à 25oC (classe I) et celles qui suppriment ce phénotypes seulement à 20oC (classe II). La mutation dsc-4 chez le nématode (impliqué dans l'assemblage des lipoprotéines) ainsi que la mutation dsc-3 (impliqué dans le métabolisme des molécules de type bile) agissent comme suppresseurs de classe I. Chacune de ces deux mutations restaure la capacité des mutants clk-1 à réagir à des changements de température. Dans cette étude, nous avons identifié un nouveau suppresseur de classe I, pgp-2 et classifié sod-4 comme étant un suppresseur de classe II. pgp-2 encode une protéine essentielle à la biosynthèse des organelles intestinales de type lysosome. Les mutations pgp-2 et sod-4 combinées ne suffisent pas à restaurer la capacité de clk-1 à répondre aux changements de température. La combinaison de différentes mutations de classe I ainsi que des mutations de classe I et la mutation de classe II, sod-4, nous a démontré que les interactions génétiques entre les différents mutants sont difficiles à prévoir.

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29

Barman, Soumi. "Construction and Senescence Phenotype Analysis of Double Mutants Encoding H3K4me3 Methyltransferases in Arabidopsis thaliana." Thesis, California State University, Long Beach, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10257592.

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Leaf senescence, which is the final process of leaf development, involves a complex regulation of thousands of genes to recover and recycle valuable nutrients and mobilize them to growing part of the plant for high yield of fruits and grains. A greater understanding of the complex senescence gene regulation could be helpful for higher crop yield. This study is focused on three genes (ATX1, ATX3 and ATX4) that code for H3K4me3 methyl transferases to investigate their effect on flowering transition time, and their importance during senescence by assaying total chlorophyll and protein levels, and quantifying the mRNA expression of senescence marker gene WRKY75. An additive early flowering phenotype was observed for double mutants. However, no senescence alteration was found for double mutants. An increased level of total chlorophyll was shown by single mutant atx4. Significant differences for total protein were observed in leaf 6 vs. leaf 7 for double mutants atx1atx3 and atx1atx4, suggesting a faster protein degradation rate or smaller variability (reduced confidence interval) in leaf 7 data. Due to the gene redundancy of the ten-member ATX family, knocking out two genes may not adequately affect the function of H3K4 methyltransferase activity. Therefore, phenotypic analyses of triple and quadruple mutants of senescence-expressed H3K4me3 methyltransferase coding genes may show stronger senescence phenotypes. Of importance, these data show that significantly early flowering does not dictate early leaf senescence.

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30

Lam, Sonya Hoan Linh. "Neu tyrosine autophosphorylation site mutants exhibit similar and distinct mammary tumour phenotypes." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112529.

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ErbB2/Neu overexpression is observed in 20--30% of human mammary carcinomas and correlates with poor prognosis. We have demonstrated that four ErbB2/Neu tyrosine autophosphorylation sites (YB, YC, YD and YE) are sufficient to mediate transforming signals in vitro and bind distinct adapter proteins, suggesting that transformation functions through distinct pathways. To study the role of each individual tyrosine autophosphorylation site in mammary tumourigenesis, we derived transgenic mice expressing mutant ErbB2/Neu receptors in the mammary gland. Recently, we showed that YB and YD female transgenic mice developed mammary tumours with differences in tumour latency, morphology, and metastatic potential. To further understand the role of the autophosphorylation sites, I characterized the YC and YE transgenic mouse models and showed that although, they exhibit similar phenotypes, they also differ in their latency, morphology and metastatic rate compared to the YB and YD transgenic mouse models. This suggests that recruitment of specific adaptor proteins has distinct biological effects on ErbB2/Neu-mediated mammary tumourigenesis.

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31

Sanderson, Micheline. "Genetic and phenotypic characterisation of an Arabidopsis thaliana jasmonic acid signalling mutant, jam2." Master's thesis, University of Cape Town, 2003. http://hdl.handle.net/11427/8590.

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Bibliography: leaves 72-77.
Jasmonic acid (JA) is a plant hormone with diverse functions, ranging from development to stress responses. Moreover, a role for JA in mediating defence against pathogen attack has been established, seemingly specific against necrotrophic pathogens such as Botrytis cinerea. Despite these known roles of JA, it is not known exactly how JA activated downstream responses, such as induced gene expression. To further our understanding of JA signalling, this work aimed to identify new components involved in JA signal transduction. A novel screening method based on lack of anthocyanin accumulation after exogenous application of the methyl ester of JA, methyl jasmonate (MeJA), was employed. A recessive, monogenic mutant, jasmonic acid modified2 (jam2), was isolated from T-DNA activation tagged lines and characterized genetically and phenotypically. jam2 was found not to be T-DNA tagged as the T-DNA segregates independently of the mutation. jam2 is unlikely to be an anthocyanin biosynthetic mutant but shows delayed anthocyanin accumulation after exogenous MeJA treatment. Resistance to MeJA root growth inhibition is a phenotype shared by all JA insensitive mutants. Contrary to this, jam2, like Col-0, exhibits stunted root growth on MeJA. The expression of the antifungal peptide, PDF1.2 can be induced by exogenous MeJA treatment. To assess how PDF1.2 expression was affected in jam2, plants were treated with external liquid and vaporous MeJA. Interestingly, the PDF1.2 expression pattern after MeJA application (liquid or gaseous) was biphasic for Col-0, jam2 and jar1. However, compared to Col-0 and jar1, jam2 appeared to be affected in the first induction peak upon liquid MeJA treatment, whilst in the second after gaseous treatment. PDF1.2 expression can also be seen as a marker for JA-mediated defence responses. Upon infection with B. cinerea, jam2 and jar1 showed intermediate resistance and faster PDF1.2 expression, compared to Col-0 and coil-1. These findings suggest that jam2 is possibly involved in temporal regulation of anthocyanin accumulation and PDF1.2 expression after MeJA application and B. cinerea infection. Therefore, jam2 may define a novel component within the JA signalling pathway and further genetic and phenotypic characterisation could confirm this.

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32

Collins, Emma Alice Maria. "Characterisation of in vivo and in vitro phenotypes of Pseudomonas aeruginosa elastase mutants." Thesis, Queen Mary, University of London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.522328.

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33

Kumar, Sudhir. "Molecular genetic and phenotypic analysis of ENU-induced mutant mouse models for biomedical research." Diss., lmu, 2011. http://nbn-resolving.de/urn:nbn:de:bvb:19-134175.

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34

Mackenzie, Francesca Emily. "Positional cloning and phenotypic characterisation of the novel hearing-impaired mouse mutant Cloth-ears." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.442824.

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35

Canas, Simoes Mariana. "Molecular genetic and phenotypic analysis of a new C. elegans MAB mutant, mab-29." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670160.

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36

Hoslin, Angela. "Genetic and phenotypic characterisation of a novel Efl1 mouse mutant of Shwachman Diamond syndrome." Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:78fdeb8d-ed5c-4bc7-aca2-e71c50df49a0.

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A novel mouse mutant was identified through an ENU (N-ethyl-N-nitrosourea) mutagenesis screen due to an abnormal gait. Next generation sequencing revealed the causative mutation to be in the gene Efl1 (K983R). The protein EFL1 is involved in ribosome maturation, a cellular process that is defective in diseases collectively known as ribosomopathies. More specifically, EFL1 is critical for the release of anti-association factor eIF6 from the 60S subunit, which allows subsequent joining with the 40S subunit to form a translationally active particle. Shwachman Diamond syndrome (SDS) is a ribosomopathy in which this process is known to be defective. SDS is an autosomal recessive disorder typified by bone marrow failure, pancreatic insufficiency and various anaemias. 90% of patients with SDS have missense mutations in the gene SBDS. The protein SBDS, together with EFL1, binds to the 60S subunit and causes the release of the anti-association factor eIF6. Both SBDS and EFL1 are needed for this process to occur correctly. In patients with SDS, eIF6 release is impaired due to a deficiency of functional SBDS, thus causing a ribosomal joining defect. Current research into SDS focuses on yeast models or conditional knockout/embryonic mouse models. However, this gives a limited view of the disorder as it does not reflect the multi-system nature or temporal aspects of SDS. In depth phenotypic characterisation of the Efl1-K983R mouse-line has revealed many phenotypes that reflect human SDS symptoms, such as small size, various haematological abnormalities, reduced bone mass density, deafness secondary to otitis media and behavioural deviations. At the molecular level, impaired eIF6 release has been demonstrated in mouse embryonic fibroblasts and liver. Multiple tissues from mutant mice show severe EFL-1 deficiency, suggesting that these symptoms may be reflective of the SBDS deficiency seen in SDS patients. Approximately 10% of SDS patients do not have SBDS mutations, and these patients are referred to as having 'genetically undefined' SDS. The cause of patients symptoms in these cases are unclear, and no causative gene has been found. Here we present data that suggests that Efl1 may be a candidate gene for 'genetically undefined' SDS. The data presented here also suggests that this mouse represents an opportunity to study SDS-like processes in a long lived, multi-system mammalian model, which is otherwise unavailable for Sbds mutants.

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37

Tona, Risa. "The Phenotypic Landscape of a Tbc1d24 Mutant Mouse Includes Convulsive Seizures Resembling Human Early Infantile Epileptic Encephalopathy." Kyoto University, 2019. http://hdl.handle.net/2433/242396.

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38

Leyser, Henrietta Miriam Ottoline. "An analysis of fasciated mutants of Arabidopsis thaliana and the role of cytokinin in this phenotype." Thesis, University of Cambridge, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357803.

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39

Gazzard, James. "Genetic and phenotypic analysis of five alleles of the mutant mouse shaker-with-syndactylism (sy)." Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342067.

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40

Wang, An-Li [Verfasser]. "Behavioral phenotypes of a transgenic rat overexpressing the full-length non-mutant human DISC1 gene / An-Li Wang." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2018. http://d-nb.info/1161182756/34.

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41

Rodrigues, Tania 1979. "Identification and analysis of new mutations that suppress the slow defecation phenotype of clk-1(qm30) mutants." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98781.

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Mutations in the clk-1 gene of Caenorhabditis elegans result in an average slowing down and deregulation of a variety of developmental and physiological processes. In addition, clk-1 mutants are defective in responding to temperature changes. For example, wild-type worms adjust their defecation cycle length after a temperature shift whereas the defecation cycle length of clk-1 mutants is unaffected by such a shift. To understand the basis of the clk-1 phenotype, a number of genetic screens have been carried out to isolate feature-specific suppressor mutations. dsc-3(qm179) and dsc-4(qm182) were isolated in this manner. It has previously been found that dsc-3(qm179) and dsc-4(qm182) strongly suppress the slow defecation phenotype of clk-1 mutants at 20°C, as well as after a temperature shift to 25°C. Molecular analysis of dsc-4, which encodes the microsomal triglyceride transfer protein, suggests that dsc genes affect lipid metabolism. We carried out a genetic screen for additional mutations that can suppress the slow defecation of clk-1 mutants after a temperature shift to 25°C and isolated two new suppressor mutations. Complementation tests as well as linkage analysis and mapping indicates that dsc-6(qm192) and dsc-7(qm193) define new dsc genes. We analyzed the phenotype of the new suppressor strains and have found that, like dsc-4(qm182), dsc-6(qm192) and dsc-7(qm193) can suppress a variety of clk-1 phenotypes. Based on additional phenotypic analyses of the new suppressor strains, including the determination of their sensitivity to exogenous cholesterol, we believe that, like dsc-4, dsc-6 and dsc-7 encode activities that affect lipid metabolism in worms.

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42

Underwood, M. I. "The relationship between ADAMTS13 genotype and phenotype in congenital thrombotic thrombocytopenic purpura and characterisation of ADAMTS13 mutants." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1462706/.

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Congenital thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy, usually involving ADAMTS13 gene defects. ADAMTS13 processes the multimeric plasma glycoprotein Von Willebrand factor making it less reactive to platelets. Patients differ in terms of disease severity and evidence suggests a relationship between ADAMTS13 genotype and disease phenotype. Over 140 mutations have been identified in patients but only ~30% of these has been expressed in vitro. The aim of this thesis was to study certain ADAMTS13 mutations identified in a homozygous form in congenital TTP patients to assess in vitro their effect on the secretion and activity of ADAMTS13 and to assess their contribution to disease phenotype. ADAMTS13 mutants (p.R102H, p.I143T and p.Y570C) and wild type (WT) were expressed in HEK293T cells. The p.R102H mutation partially affected the secretion of ADAMTS13 and reduced the catalytic efficiency of the mutant but not to the extent predicted based upon levels measured in patient plasma. Expressing this mutant with three ADAMTS13 polymorphisms (p.Q448E, p.P618A and p.A900V) which were also identified in the patient with this mutation further reduced the secretion and activity of ADAMTS13. When these three polymorphisms were expressed separately in WT ADAMTS13, the p.P618A polymorphism reduced the secretion and subsequently the activity of ADAMTS13 suggesting that this polymorphism in particular was responsible for the reduction observed. These results highlight the importance of ADAMTS13 polymorphisms. The p.I143T and p.Y570C mutations severely affected ADAMTS13 secretion. Immunofluorescence studies showed localisation of these mutants within the ER but less extensive localisation within the cis Golgi compared to WT ADAMTS13. The p.I143T mutant was characterised further and was shown to be degraded by the cell proteasome. Addition of a chemical chaperone (betaine) appeared to rescue the secretion defect caused by the p.I143T mutation. This may have future therapeutic implications for the treatment of some congenital TTP patients.

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43

Nakouzi, Ghunwa Akram. "Genetic and Phenotypic Response of Neural Tube Defect Mouse Mutants to Folic Acid." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1246538783.

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44

Dilling, Bradley Paul. "Mapping and phenotypic characterization of temperature sensitive vaccinia virus mutants cts6 and cts9." [Gainesville, Fla.] : University of Florida, 2004. http://purl.fcla.edu/fcla/etd/UFE0004844.

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Thesis (M.S.)--University of Florida, 2004.
Typescript. Title from title page of source document. Document formatted into pages; contains 51 pages. Includes Vita. Includes bibliographical references.

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45

Kesavan, Jayati. "Genetic analysis and phenotypic characterization of two Shewanella putrefaciens iron reduction-deficient mutants." Thesis, Georgia Institute of Technology, 1998. http://hdl.handle.net/1853/25231.

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46

Wahab, Adbul. "Regulation of antibiotic production in Streptomyces coelicolor : phenotypic and transcriptomic analysis of AbsA mutants." Thesis, University of Surrey, 2007. http://epubs.surrey.ac.uk/843422/.

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The AbsA two-component system is a negative regulator of antibiotic biosynthesis in Streptomyces coelicolor. To gain further insight into the role of the AbsA system different in-frame deletion mutations were made in the absA1A2 operon in S. coelicolor MT1110, MT1110DeltacdaR and S. lividans 1326. Phenotypic analysis of DeltaabsA1A2 and DeltaabsA2 in the MT1110 derivatives showed that CDA was produced early on Oxoid nutrient agar relative to the parent strain. The absA mutants in S. lividans 1326 (both DeltaabsA1 and DeltaabsA1A2) did not show early CDA production. On solid R2YE both MT1110DeltaabsA1A2 and MT1110DeltaabsA2 produced undecylprodigiosin and actinorhodin earlier. In liquid R2YE medium MT1110DeltaabsA1A2 produced undecylprodigiosin and actinorhodin earlier compared to MT1110 wild-type. RNA was extracted from surface-grown cultures of MT1110 and its DeltaabsA1A2 derivative on R2YE agar at different stages of growth. Cy3-labelled cDNA and Cy5-labelled genomic DNA (gDNA) were hybridised on in-house printed 50-mer oligo arrays representing all S. coelicolor open reading frames. Differentially expressed genes were identified by the 'Rank Product' method. Transcriptomic analysis revealed that many genes encoding enzymes of central metabolism were up-regulated in MT1110DeltaabsA1A2 compared to MT1110 wild-type. Three genes, SCO4089, SCO3829 and SCO1270 encoding valine dehydrogenase, dihydrolipoamide acyltransferase component E2 and the alpha-subunit of pyruvate dehydrogenase complex respectively, were found to be more highly expressed in MT1110DeltaabsA1A2. These genes encode enzymes whose reactions produce possibly precursors for CDA, Act and Red biosynthesis. The gene encoding pyruvate kinase 2 (SCO5423) showed increased expression in the mutant at and after 24 h of growth. Genes encoding subunits of ATP synthases showed increased expression in the mutant that indicates that an increase oxidative metabolism is occurring in MT1110DeltaabsA1A2. A gene, SCO6195, encoding a stationary phase-active enzyme, acyl-coenzyme A synthetase was induced in MT1110DeltaabsA1A2 at 23 and 24 h of cultivation. Two genes in the cda cluster were found to be repressed in mutant: SCO3224 and SCO3229, encoding an ABC transporter ATP-binding protein and 4-hydroxymandelate synthase, respectively. The gene encoding AfsS (SCO4425) was found to be up-regulated in the DeltaabsA1A2 mutant at the late phase of the growth. Four genes encoding enzymes putatively involved in the pentose phosphate pathway were found to be up-regulated in MT1110DeltaabsA1A2 at certain time points. Genes encoding ribosomal protein showed a more relaxed growth phase dependent pattern of expression in the mutant while one r- protein encoding gene, rpsK (SCO4728), showed higher expression in the mutant except at stationary phase. It is deduced from the global gene expression analysis that the possible role of the AbsA system in S. coelicolor is to regulate precursor supply for antibiotic production rather than to directly regulate the genes of the respective antibiotic biosynthetic clusters.

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47

Hawkins, Thomas. "The control of central nervous system myelination and the phenotypic characterisation of a novel zebrafish mutant, akineto(u45)." Thesis, University College London (University of London), 2004. http://discovery.ucl.ac.uk/1446716/.

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Part 1 of this thesis addresses the control of myelination in the central nervous system (CNS). We have a sound knowledge of myelin structure, particularly the molecules and cells involved in its make-up. However, our understanding of the control of myelin formation is scanty. Myelination of CNS tracts during development follows a strictly ordered schedule suggesting local control by axons. Here I present evidence that CNS axons need to form synaptic connections before they can be myelinated. I have used myelin renewal during regeneration of the fish optic nerve as a model system: the axons withstand target deprivation and their behaviour in these circumstances is well characterised from earlier studies of synaptic plasticity. Depriving the regenerating optic nerve of its primary target, the contralateral optic tectum, delays myelination until the regenerating axons find the intact ipsilateral tectum and form synapses there. Facilitating this process hastens the onset of myelination and denying the axons of any opportunity to form synapses abolishes it. I investigated possible mechanisms by which the synaptogenesis-timed signal is mediated and also compared myelination during regeneration and development. Part 2 describes the phenotypic characterisation of a novel zebrafish mutant: akineto (aknu45). Aknu45 mutant embryos cannot contract their skeletal muscles. Here I show that this is caused by incomplete sarcomere assembly. Myofibrils of mutants lack properly assembled thick filaments. Our understanding of the process of myofibrillogenesis, particularly relating to thick filament assembly, is mostly speculative at present. Although the aknu45 gene is unidentified so far, I am currently engaged in efforts to identify it. Subsequently the aknu45 mutation may become a useful tool to further unravel the process of myofibrillogenesis.

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Kumar, Sudhir [Verfasser], and Bernhard [Akademischer Betreuer] Aigner. "Molecular genetic and phenotypic analysis of ENU-induced mutant mouse models for biomedical research / Sudhir Kumar. Betreuer: Bernhard Aigner." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2011. http://d-nb.info/1015203213/34.

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McPhee, Scott William John. "Phenotypic characterisation of the tremor mutant and AAV mediated aspartoacylase gene transfer in the rat model of Canavan disease." Thesis, University of Auckland, 2004. http://wwwlib.umi.com/dissertations/fullcit/3136372.

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The doctoral studies described in this thesis involve the phenotypic characterization of the tremor rat, an animal model of Canavan disease, and a proof of principle gene transfer study in this model. The phenotype of the tremor rat is examined at the genetic, molecular, cellular, neurochemical, physical and behavioural levels, and tremor mutants are described within the context of Canavan disease. Tremor mutants appear to share many phenotypes with both human patients and to the knock-out mouse model. The deletion of aspartoacylase results in a total loss of the capacity to metabolize N-acetyl-aspartate to acetate and aspartate in brain, leading to elevations in brain N-acetyl-aspartate levels, changes in cell and tissue morphology, and physical and behavioural deficits including mild akinesia and loss of normal motor coordination and balance. Parallel to this work was the development of a gene transfer approach to treat Canavan disease, involving Adeno-associated virus mediated delivery of aspartoacylase to the mammalian central nervous system. Gene transfer was undertaken in tremor rat mutants, and analysis was made of gene expression and function as well as the effect of aspartoacylase expression on improving the phenotypic deficits observed in mutant animals. Gene expression was observed at the RNA and protein level, with recombinant protein observed in cell soma and processes. Although not significant the data suggested a trend of decreased NAA levels after aspartoacylase transfer in comparison to animals injected with a vector encoding green fluorescent protein. Improvement was noted in the rotorod phenotype with mutant animals receiving aspartoacylase gene transfer performing better at tests of balance and coordinated locomotion than animals receiving a control vector. The study provided evidence that Adeno-associated virus mediated aspartoacylase gene transfer to the brain improves some of the deficits in tremor mutants, and supports the rationale of human gene transfer for Canavan disease.
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Mangoli, Maryam. "Molecular and phenotypic characterisation of zebrafish mutants displaying defects in axonal development in the central nervius system." Thesis, University College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408677.

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Dissertations / Theses on the topic 'Mutant Phenotype'

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