Molecular characterization of a radiation-induced reverse mutation at the dilute locus in the mouse

Irradiation has been employed successfully to increase the reverse mutation rate at the agouti and dilute loci in the mouse. The dilute allele has previously been shown to be due to the insertion of an ecotropic-specific murine leukaemia virus in the vicinity of the dilute locus, and its instability to be due to the excision of the proviral sequence (Jenkins et al. 1981). Molecular analysis of the recovered radiation-induced revertant at the dilute locus indicated excision of all but approximately 500 bp of the proviral sequence. The proviral sequence remaining in the mouse genome hybridizes to a probe specific for the proviral long terminal repeat (LTR) sequence. Previous characterization of two spontaneous reverse dilute mutations indicated precise proviral excision of all but a single LTR, and suggests homologous recombination between the proviral LTR sequences as the mechanism of proviral excision (Hutchison, Copeland & Jenkins 1984). The present results indicate that radiation and increases the reverse mutation rate at the dilute locus acts by a similar mechanism, and suggest that mutagenic treatment may be employed to produce genetic variants of interest.