MOLECULAR ANALYSIS OF VIABLE SPONTANEOUS AND RADIATION-INDUCED ALBINO (C)-LOCUS MUTATIONS IN THE MOUSE

Thirty-one homozygous-viable, radiation-induced or spontaneous mutations at the albino (c) locus in mouse chromosome 7 were analyzed by Southern blot analysis with a tyrosinase cDNA clone and with probes derived from the closely linked proviral integration sites Pmv-31 and Emv-23, which flank the tyrosinase gene on the proximal and distal sides, respectively. Thirteen of 27 radiation-induced and one of four spontaneous mutations manifested deletions or rearrangements for the tyrosinase gene. The sizes of four deletions found to break within the tyrosinase gene itself were estimated to be less-than-or-equal-to 36 kb, less-than-or-equal-to 40 kb, approximately 260 kb, and approximately 480 kb. Two homozygous-viable deletions were found to include flanking proviral loci, suggesting that they could be from 1500-2000 kb in length, if not longer. The existence of these very large, homozygous-viable deletions suggests that the one-to-two megabases including and surrounding the c locus harbor no genes essential for normal viablility or fertility, although genes controlling more subtle (or ''nonessential'') phenotypes are likely to be present. These data thus provide some insight into the molecular structure of a number of viable c-locus mutations, whose nature could not be predicted solely on the basis of genetic analysis, as could be done for either lethal or reduced-pigment c mutations.