Somatic and germ-line reverse mutation rates of the retrovirus-induced dilute coat-color mutation of DBA mice

Abstract

At present, the dilute (d(v)) coat-color mutation of DBA mice provides the only simple means for measuring the relative somatic and germ-line reverse mutation rates of retrovirus-induced mutations in mammals. The d(v) mutation was generated by the spontaneous integration of an ecotropic murine leukemia virus into noncoding sequences of the dilute locus. Reversion of the d(v) mutation occurs by provirus excision and is mediated by homologous recombination events involving the viral long terminal repeat sequences. Although numerous independent germ-line d+ revertants have been identified, somatic d+ revertants have not been reported previously. During the past 5 years, we have screened more than one million mice homozygous for the d(v) mutation to determine whether we could identify somatic d+ revertants. This survey has resulted in the identification of a somatic d+ revertant and has provided a data base from which we can estimate the relative somatic and germ-line excision frequencies of retroviruses in mice and speculate about the nature of homologous recombination events producing d+ revertant alleles.