International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

H7 Evaluation of Neurological Mouse Mutants Caused by ENU Mutagenesis

A. Isaacs1, A. Potter1, M. Masih1, L. Vizor2, K. E. Davies1, J. Peters2, P. Nolan2, J. E. Martin3, F. S. Walsh4, S. D. M. Brown2, and A. J. Hunter4. 1Dept of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK; 2MRC Mammalian Genetics Unit, Harwell, UK; 3Dept of Histopathology and Morbid Anatomy, Queen Mary and Westfield College, Mile End Road, London E1 4NS, UK; 4Dept of Neuroscience, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park (North), Third Avenue, Harlow, Essex CM19 5AW, UK

The importance of mutant phenotypes for characterising gene function has been amply shown in lower organisms. Given that mouse mutants are available for only 1-2% of all mouse genes, there is a real need to improve the mutant mouse resource. We are therefore embarking upon a large scale, genome wide, phenotype driven ENU mutagenesis screen for dominant mutations in the mouse. The SHIRPA behavioural and functional mouse phenotype assessment protocol is being used to identify mutant phenotypes. A secondary histological screen of muscle (four hind limb muscles, diaphragm and heart) of mutants with potential motor defects, used a combination of general cellular staining with Heamatoxylin and Eosin (H and E), and fibre type analysis with NADH-TR and ATPase, to identify myopathy or denervation. Muscle from 19 mouse lines was analysed covering a range of abnormalities picked up by the SHIRPA protocol, including, abnormal gait, poor wire manoeuvre, low grip strength, low locomotor activity and low limb tone, however no abnormal pathology was found. In a histological screen of tremor mutants, peripheral nerve sections were analysed using toludine blue staining, and sections throughout the brain, and lumbar and cervical enlargements of the spinal cord were analysed using H and E, Cresyl Violet, and Luxol fast blue staining. 3 mouse lines were screened, 2 with resting tremor, and one with hindleg kinetic tremor. The only abnormal pathology noted was severe loss of peripheral nerve myelin in both resting tremor lines. Loss of peripheral nerve myelin has previously been reported in mice which tremor. These two new mutant lines may provide new insight into the pathology of tremors.

 


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