MOLECULAR-GENETICS OF THE BROWN (B)-LOCUS REGION OF MOUSE CHROMOSOME-4 .1. ORIGIN AND MOLECULAR MAPPING OF RADIATION-INDUCED AND CHEMICAL-INDUCED LETHAL BROWN DELETIONS

Over a period of many years, germ-cell mutagenesis experiments using t he mouse specific-locus test have generated numerous radiation- and ch emical-induced alleles of the brown (b; Tyrp1) locus in mouse chromoso me 4. We describe here the origin, maintenance and initial molecular c haracterization of 28 b mutations that are prenatally lethal when homo zygous. Each of these mutations is deleted for Tyrp1 sequences, and ea ch of 25 mutations tested further is deleted for at least one other lo cus defined by molecular clones previously found to be closely linked to b by interspecific backcross analysis. A panel of DNAs from mice ca rrying a lethal b mutation and a Mus spretus chromosome 4 was used in the fine structure mapping of these molecularly defined loci. The dele tional nature of each of these prenatally lethal mutations is consiste nt with the hypothesis that the null phenotype at b has an effect only on the quality (color) of eumelanin produced in melanocytes. The resu lting deletion map provides a framework on which to build future molec ular-genetic and biological analyses of this region of mouse chromosom e 4.