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.
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Acknowledgment
We thank Walderico Generoso for providing the original translocation lines and for ongoing advice, and K.T. Cain and Nestor Cacheiro for expert phenotypic and karyotypic analysis of the mutants. We also thank our colleagues at LLNL for their support, including Ivan Ovcharenko for bioinformatics and identifying the set of large genes for our discussion, and Nicole Collette for comments on the manuscript. This work was completed under the auspices of the US Department of Energy, Office of Biological and Environmental Research, by the University of California, Lawrence Livermore National Laboratory under contract number W-7405-Eng-48.
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Robinson, K.O., Petersen, A.M., Morrison, S.N. et al. Two reciprocal translocations provide new clues to the high mutability of the Grid2 locus. Mamm Genome 16, 32–40 (2005). https://doi.org/10.1007/s00335-004-2423-z
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DOI: https://doi.org/10.1007/s00335-004-2423-z