Two reciprocal translocations provide new clues to the high mutability of the Grid2 locus.

ABSTRACT

We describe two new mutations, 153Gso and 154Gso, associated with reciprocal translocations with a common breakpoint in mouse chromosome 6B3 (Mmu6B3). The translocations arose independently in offspring of male mice treated with chlorambucil and glycidamide, respectively. Homozygotes of both mutant stocks display a characteristic gait ataxia with 'foot-patting' behavior; despite their ataxia the mutant animals are healthy, long-lived, and breed normally. Breeding experiments confirmed that 153Gso and 154Gso mutations are allelic, and both fail to complement a known mutation hotfoot (ho), a Mmu6 mutation involving the glutamate receptor gene, Grid2, that is associated with a virtually identical phenotype. Our studies demonstrate that the 153Gso and 154Gso mutations disrupt the Grid2 gene at sites located more than 100 kb apart in intron 6 and intron 4 of the gene, respectively. The occurrence of two independent translocations from a relatively small colony within the same locus supports data suggesting the hypermutability of the Grid2 locus and suggest that the gene's large size make it an especially likely target for mutations involving genetic rearrangement.