Genetic Organization of the agouti Region of the Mouse

Linda D. Siracusa ¹, Liane B. Russell ², Eva M. Eicher ³, Dorcas J. Corrow ³, Neal G. Copeland ¹, and Nancy A. Jenkins ¹

¹ Mammalian Genetics Laboratory, BRI-Basic Research Program, NCI-Frederick Cancer Research Facility, Frederick, Maryland 21701
² Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830
³ The Jackson Laboratory, Bar Harbor, Maine 04609

The agouti locus on mouse chromosome 2 acts via the hair follicle to control the melanic type and distribution of hair pigments. The diverse phenotypes associated with various agouti mutations have led to speculation about the organization of the agouti locus. Earlier studies indicated that two presumed agouti alleles, lethal yellow (A^y) and lethal light-bellied nonagouti (a^x), are pseudoallelic. We present genetic data showing probable recombination between A^y and three agouti mutations (a^t, a, and a^x), which suggest that A^y is a pseudoallele of the agouti locus. The close linkage of an endogenous ecotropic murine leukemia provirus, Emv-15, to A^y provides a molecular access to genes at or near the agouti locus. However, previous studies suggested that the Emv-15 locus can recombine with some agouti alleles and therefore we analyzed mice from recombinant inbred strains and backcrosses to measure the genetic distance between various agouti alleles and the Emv-15 locus. Our data indicate that the Emv-15 locus is less than 0.3 cM from the agouti locus. These experiments provide a conceptual framework for initiating chromosome walking experiments designed to retrieve sequences from the agouti locus and give new insight into the genetic organization of the agouti region.

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