HOTFOOT MOUSE MUTATIONS AFFECT THE DELTA-2 GLUTAMATE-RECEPTOR GENE AND ARE ALLELIC TO LURCHER

Hotfoot (ho) is a recessive mouse mutation characterized by cerebellar ataxia associated with relatively mild abnormalities of the cerebellu m. It has been previously mapped to Chromosome 6, and at least eight i ndependent alleles have been reported. Here we show that the hotfoot p henotype is associated with mutations in the glutamate receptor ionotr opic delta 2 gene (Grid2). We have identified a 510-bp deletion in the Grid2 coding sequence in the ho(4J) allele, resulting in a deletion o f 170 amino acids of the extracellular domain of the receptor. Analysi s of a second allele, ho(TgN37INRA) revealed a 4-kb deletion in the Gr id2 transcript. The GRID2 protein in these hotfoot mutants probably ha s a reduced (or null) activity since the phenotype of hotfoot bears si milarities with the previously described phenotype of Grid2 knockout m ice. The exceptionally high number of independent alleles at the ho lo cus is an invaluable tool for investigating the function of the glutam ate receptor ionotropic delta 2 protein, which so far remains largely unknown. (C) 1998 Academic Press.