International Mammalian Genome Society

F43 Characterisation of a Mouse Model of Neuromuscular Disease Generated by Transgenic Insertional Mutagenesis

Derek Paisley and Andrew Ward. Developmental Biology Programme, School of Biology and Biochemistry, University of Bath, Bath, U.K.

In a screen of 78 lines of transgenic mice for insertional mutant phenotypes, amongst a number of lines identified, one displayed a striking neuromuscular disorder.

Homozygotes are smaller than their siblings, exhibit progressive ataxia and tremor, have cerebellums of reduced size and die between P19 and P25. A combination of Fluoresence In-Situ Hybridisation (FISH) and genetic mapping with microsatellite markers has located the, multiple copy, transgene array at the mid-region of chromosome 4.

Several candidiate genes are present in this region, two of which; the glycine transporter 1 (glyt1) and fatty acid amide hydrolase (Faah) genes, have been shown to be expressed at normal levels in mutant animals. A third, the disabled homologue 1 (mDab1) gene, is being tested. Previously characterised mDab1 mutants display a remarkably similar phenotype to our line, making this another likely candidate.