Fine mapping of the friend retrovirus resistance gene, Rfv3, on mouse chromosome 15

Rfv3 is a host resistance gene that operates through an unknown mechanism t o control the development of the virus-neutralizing antibody response requi red for recovery from infection with Friend retrovirus. The Rfv3 gene was p reviously mapped to an approximately 20-centimorgan (cM) region of chromoso me 15. More refined mapping was not possible, due to a lack of microsatelli te markers and leakiness in the Rfv3 phenotype, which prevented definitive phenotyping of individual recombinant mice. In the present study, we overca me these difficulties by taking advantage of seven new microsatellite marke rs in the Rfv3 region and by using progeny tests to accurately determine th e Rfv3 phenotype of recombinant mice. Detailed linkage analysis of relevant crossovers narrowed the location of Rfv3 to a 0.83-cM region. Mapping of c losely linked genes in an interspecific backcross panel allowed us to exclu de two previous candidate genes, Ly6 and Wnt7b. These studies also showed f or the first time that the Hsf1 gene maps to the Rfv3-linked cluster of gen es including Il2rb, Il3rb, and Pdgfb. This localization of Rfv3 to a region of less than 1 cM now makes it feasible to attempt the cloning of Rfv3 by physical methods.