Transgene-induced mutation of the murine steel locus

Abstract

The product of the steel locus is essential for normal development of three distinct populations of stem cells--the neural crest-derived melanoblasts, germ cells, and blood cell precursors. Many mutant alleles at steel are lethal in homozygotes and produce coat color dilution in heterozygotes. We have identified a transgenic mouse with diluted pigmentation that closely resembles that of steel heterozygotes. We have demonstrated that the site of transgene insertion is genetically linked to the phenylalanine hydroxylase locus on mouse chromosome 10. In addition, the chromosome carrying the transgene fails to complement the recessive lethality of the Sl allele of steel and the pigmentation defect of the Slpan allele. The data indicate that the inserted transgene has disrupted the steel locus. The resulting allele, designated Sltg, provides a molecular tag for isolation of the steel gene, as well as a new allele for characterization of this developmentally important locus.