title: Analysis of human neurological disorders using mutagenesis in the mouse.
abstract: The mouse continues to play a vital role in the deciphering of mammalian gene function and the modelling of human neurological disease. Advances in gene targeting technologies have facilitated the efficiency of generating new mouse mutants, although this valuable resource has rapidly expanded in recent years due to a number of major random mutagenesis programmes. The phenotype-driven mutagenesis screen at the MRC Mammalian Genetics Unit has generated a significant number of mice with potential neurological defects, and our aim has been to characterize selected mutants on a pathological and molecular level. Four lines are discussed, one displaying late-onset ataxia caused by Purkinje cell loss and an allelic series of three tremor mutants suffering from hypomyelination of the peripheral nerve. Molecular analysis of the causative mutation in each case has provided new insights into functional aspects of the mutated proteins, illustrating the power of mutagenesis screens to generate both novel and clinically relevant disease models.
authors.affiliation: MRC Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Oliver
authors.forename: Kay E
authors.initials: KE
authors.lastname: Davies
mesh_terms: D000818:Animals; D002524:Cerebellar Ataxia / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D016296:Mutagenesis; D009185:Myelin Proteins / Q000235:genetics; D009422:Nervous System Diseases / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010523:Peripheral Nervous System Diseases / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins
chemical_list: C485619:Gtf2a1lf protein, mouse; D009185:Myelin Proteins; D009687:Nuclear Proteins; C489545:Pmp22 protein, mouse; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins