The albino locus in the laboratory mouse Mus Musculus : analysis by somatic cell genetics and interspecies meiotic recombination

Homozygous deletion of the c-locus region of mouse chromosome 7 results in embryonic lethality. A major focus of the thesis was to develop experimental approaches for the study of large c-locus deletions at the DNA level which deal with the difficulties posed by homozygous lethality. Two approaches were developed: (1) Construction of somatic cell hybrids carrying a large, lethal deletion of the c-locus and (2) Generation of F₁ animals from Mus musculus deletion stocks mated to the wild-type feral mouse Mus spretus. Five somatic cell hybrids were obtained that segregated the normal mouse chromosome 7, uncovering the sequences deleted in c^26DVT chromosome 7 retained. Mus musculus × Mus spretus F₁ animals carrying the c^14CoS, c ^146G ,c ^26DVT, and c ^12FR60Hb deletions were obtained. DNA obtained from these somatic cell hybrids and interspecies hybrid animals was characterized by Southern blot hybridization to a known c-locus deletion DNA sequence, clone 12A. The results demonstrated the ability of this method to reveal sequences missing in the c-deletions. This method was applied to the mouse chromosome 7 sequences, Ct, Pth, Hras-1, Ins-2, H19, and CLX18, CLX23, and 11B6-9 (three anonymous sequences selected from chromosome 7-enriched recombinant DNA libraries using mouse-specific repeats). Results suggest that none of the sequences are missing in any of the c-locus deletions.

Another goal of the thesis was to develop a detailed map of the c-locus region. The segregation of alleles was followed by analysis of RFLPs in the backcross progeny of a Mus musculus to wild-type feral mouse, Mus spretus, mating. 44 offspring of such matings were examined at six defined loci and with three anonymous DNA sequences. The segregation of alleles for these markers demonstrated linkage relationships from which a most probable gene order of:

Centromere---Ldh-1---Hras-1---c---12A---Hbb---(Ct,Pth)---CLX18---H19

was established. The linkage map of the mouse was compared with the human linkage map. The comparison suggests a minimum of four rearrangements has occurred in the divergence between mouse and man.