Clonal coat color variation due to a transforming gene expressed in melanocytes of transgenic mice.

Abstract

Transgenic mice of an inbred black strain were previously produced with the Tyr-SV40E transgene, comprising simian virus 40 transforming sequences driven by the tyrosinase promoter, in order to obtain melanomas; the animals were found to be lighter than normal in coat color, to various degrees. As described here, hypopigmentation resulted from diminished differentiation of melanized pigment granules in the melanocytes of the hair bulbs in vivo and occurred autonomously in cultured melanocytes. Whereas some of the mice had single-color coats, most (7/13) had coats of two or three colors; in addition, one single-color founder produced a two-color descendant. These eight mice had patterns seen in natural genotypes; the most striking were transversely striped to various extents, with regions of left-right asymmetry on either side of the dorsal midline. The patterns visualized the same clonal developmental territories of coat melanocytes displayed in allophenic mice that are formed from conjoined early embryo cells of different color genotypes. Some of the Tyr-SV40E transgenics were also cellular genotypic mosaics, probably arising by late integration of the transgene. However, one transgenic founder with a completely striped coat proved to be true-breeding, with autosomal inheritance of the pattern. The inherited striped pattern thus exemplifies the formation of phenotypically different but genetically identical developmental clones, or phenoclones, among cells of the same type. This line of transgenic mice provides exceptional material for experimental analysis of the molecular basis for clonal variation in gene expression and of the fate of oncogenic phenoclones of melanocytes occurring in the same individual.