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.

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.

Assignment of a gene that determines erythrocytic guanosine-5′-triphosphate concentration (Gtpc) to mouse chromosome 9

Nine inbred mouse strains surveyed for erythrocytic guanosine-5′-triphosphate (GTP) concentration were found to segregate into two discrete groups. Strains having low GTP levels between 1.4 and 3.4 nmol/109 cells were C3H/HeJ, C3H/HeHa, A/J, and WB/ReJ. Strains having high GTP levels between 11.0 and 14.8 nmol/109 cells were AKR/J, DBA/2J, CBA/J, C57BL/6J, and C57L/J. Erythrocytic ATP levels did not vary significantly among these groups. Crosses between low and high GTP strains gave F1 progeny having intermediate levels of GTP, and the progeny of F1's backcrossed to parental strains segregated in a 1:1 ratio for GTP concentration. We designated the GTP concentration determining trait, Gtpc. Typing the C57BL/6J × C3H/HeJ (B × H) recombinant inbred strains for GTP levels revealed 0/12 strain distribution pattern differences for loci on both chromosomes 5 and 9. Backcross analysis did not provide evidence for linkage of Gtpc to W (dominant white spotting) on chromosome 5 with 15/45 recombinants. A test for linkage of Gtpc to transferrin (Trf) on chromosome 9 gave evidence of linkage with an observed recombination frequency of 14.6 ± 5.5 and a 99% confidence interval of 3.9–33.9 cM.Key words: guanosine-5′-triphosphate, GTP, mouse, chromosome 9.