Molecular genetics of the brown (b)-locus region of mouse chromosome 4. I. Origin and molecular mapping of radiation- and chemical-induced lethal brown deletions.

Abstract

Over a period of many years, germ-cell mutagenesis experiments using the mouse specific-locus test have generated numerous radiation- and chemical-induced alleles of the brown (b; Tyrp 1) locus in mouse chromosome 4. We describe here the origin, maintenance and initial molecular characterization of 28 b mutations that are prenatally lethal when homozygous. Each of these mutations is deleted for Tyrp 1 sequences, and each of 25 mutations tested further is deleted for at least one other locus defined by molecular clones previously found to be closely linked to b by interspecific backcross analysis. A panel of DNAs from mice carrying a lethal b mutation and a Mus spretus chromosome 4 was used in the fine structure mapping of these molecularly defined loci. The deletional nature of each of these prenatally lethal mutations is consistent with the hypothesis that the null phenotype at b has an effect only on the quality (color) of eumelanin produced in melanocytes. The resulting deletion map provides a framework on which to build future molecular-genetic and biological analyses of this region of mouse chromosome 4.

Molecular genetics of the brown (b)-locus region of mouse chromosome 4. II. Complementation analyses of lethal brown deletions.

“…The blACRg mutation, found in this study to affect the b, baJ 1(4)2Rn, dep and 1(4)3Rn loci, had not been included in the molecular analyses presented in a companion study (RINCHIK et al 1994). Nonetheless, we were able to determine that b4ACRg is deleted for the D4Rck1401ocus, but not the D4Rck4 and D4Rck52 loci, by hybridizing Southern blots of TuqI digests of DNA prepared from b3Ypsc/b4ACRg mice obtained from the complementation crosses (Figure 3) to the relevant probes.…”

“…This type of analytical strategy has now also been applied to the wi-Ifa region of mouse chromosome 4. Heritable, lethal, radiation-or chemical-induced deletions of the brown ( b; T y r p l ) locus (RINCHIK et al 1994) are available for use as experimental reagents to map molecularly and phenotypically defined loci in the region immediately surrounding the b locus. The combined molecular and complementation map of the b region presented in Figure 6 can provide a framework on which to build future physical and mutation maps of this chromosomal segment.…”

“…Among this set of radiation-and chemical-induced b mutations are those that are lethal in homozygotes. These lethal mutations are chromosomal deletions of varying length that encompass at least a portion, if not all, of the b ( T y r p l ) locus itself (RINCHIK et al 1994).Combining genetic and molecular analyses of regions of the mouse genome that are associated with radiationor chemical-induced deletion mutations at specific loci represents a powerful strategy for developing integrated physical and functional maps for megabase stretches of the mammalian genome (reviewed in RINCHIK and RUSSELL 1990). Such studies on the dilute ( d ) region of chromosome 9 (e.g.,…”

“…Among this set of radiation-and chemical-induced b mutations are those that are lethal in homozygotes. These lethal mutations are chromosomal deletions of varying length that encompass at least a portion, if not all, of the b ( T y r p l ) locus itself (RINCHIK et al 1994).…”

“…1 and RESULTS). DNA preparation, blotting, and hybridization were carried out as described previously (RINCHIK et al 1990a(RINCHIK et al , 1994.…”