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Title: Neuroanatomical screening and analysis of transgenic and ENU induced mutagenised mice
Author: Edwards, Andrew
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2011
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I have sought to discover genetic causes of neuroanatomical defects by conducting N-ethyl-N-nitrosourea mutagenesis and transgenic knock out screens in mice. The rationale behind this is that mutations causal to structural defects will be informative about developmental neurobiology and the biological basis of behaviour. Direct screening for behavioural abnormalities in mice has historically been arduous and yielded few findings due to small effect sizes and limited statistical power. My approach sought to bypass these problems by screening for highly penetrant morphological phenotypes. This thesis details my screens and the histological, genetic and behavioural characterisation of lines of interest. These include models of hydrocephalous, pyramidal cell layer ectopia, abnormal neurogenesis, corpus callosum agenesis, hippocampal enlargement, elevated cell death and hypomyelination. Whilst N-ethyl-N-nitrosourea mutagenesis screening has been conducted since the twilight of the 20th century, systematic transgenic knock out screening is currently in its infancy. By discovering gene-phenotype associations through both approaches, I have been able to compare the relative yields, strengths and weaknesses of the two screening methods. Additionally, I have discussed the significant of the gene-phenotype associations produced from both screens.
Supervisor: Flint, Jonathan Sponsor: Le Fondation Jerome Lejeune ; Wellcome Trust ; Corpus Christi College
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medical Sciences ; Clinical genetics ; Anatomy ; Biology (medical sciences) ; Neurogenetics ; Neuropathology ; Transgenics ; Neuroscience ; Psychiatry ; Intellectual disability ; mental retardation ; neuroanatomy ; brain development ; CNS development ; gene mapping