title: 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.
authors.affiliation: Biology Division, Oak Ridge National Laboratory, Tennessee 37831-8077.
authors.forename: E M
authors.initials: EM
authors.lastname: Rinchik
authors.forename: J A
authors.initials: JA
authors.lastname: Bell
authors.forename: P R
authors.initials: PR
authors.lastname: Hunsicker
authors.forename: J M
authors.initials: JM
authors.lastname: Friedman
authors.forename: I J
authors.initials: IJ
authors.lastname: Jackson
authors.forename: L B
authors.initials: LB
authors.lastname: Russell
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002874:Chromosome Mapping / Q000379:methods*; D003433:Crosses, Genetic; D004252:DNA Mutational Analysis / Q000379:methods; D017931:DNA Primers; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D017353:Gene Deletion; D005804:Genes, Lethal; D018095:Germ-Line Mutation; D006200:Hair Color / Q000235:genetics*; D008297:Male; D008543:Melanins / Q000096:biosynthesis / Q000235:genetics; D008562:Membrane Glycoproteins; D051379:Mice / Q000235:genetics*; D008809:Mice, Inbred C3H / Q000235:genetics; D008969:Molecular Sequence Data; D009115:Muridae / Q000235:genetics; D016296:Mutagenesis; D010088:Oxidoreductases; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011506:Proteins / Q000235:genetics; D013093:Spermatogonia / Q000187:drug effects / Q000528:radiation effects
chemical_list: D017931:DNA Primers; D008543:Melanins; D008562:Membrane Glycoproteins; D011506:Proteins; C041877:eumelanin; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; C064056:tyrosinase-related protein-1; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases