International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

F46 Isolation and Characterization of a Candidate for the Mouse Hybrid Sterilitiy 6 Gene

Steve Pilder,1 John Fossella2, Sadhana Samant,1 Lee Silver.2 1Dept. of Anatomy & Cell Biology, Temple University School of Medicine, Philadelphia, PA, USA; 2Dept. of Molecular Biology, Princeton University, Princeton, NJ, USA

M.m domesticus males heterozygous for an introgressed M. spretus allele of the Chr 17-specific Hst6 locus and a t haplotype are sterile because their sperm swim aberrantly. In addition, males homozygous for this introgressed Hst6 allele are sterile because their sperm flagella fail to develop, although the gross elements that normally assemble into flagellar structures appear to be present in the spermatid cytoplasm (Pilder et al. 1993 Dev Biol 159, 631-642). Recently, the gene(s) responsible for eliciting these two phenotypes ("curlicue" and "whipless", respectively) was mapped to a < 0.2 cM sub-locus of Hst6 named Curlicue a (Ccua; Redkar et al. 1998 Mamm Genome 9, 825-830; Samant et al. 1999 Mamm Genome 10, 88-94).

In the present study, we have used differential display-PCR to isolate a cDNA fragment, Hst6.7, that recognizes an ~15 Kb message expressed in wild-type testis, but not in the testis of "whipless" animals. Simultaneously, we have cloned an ~0.4 cM contig of overlapping BACs containing the entire Ccua locus in its proximal half, and have mapped Hst6.7 to Ccua. In addition, we present evidence that Hst6.7 is the 3'-end of a testis-specifically expressed gene, Dnahc8 (Vaughan et al. 1996), encoding an axonemal dynein heavy chain. We also show that the mRNA expression characteristics displayed by Dnahc8 are consistent with its having a species-specific fundamental role in sperm flagellar development and function. Implications concerning a potential role for the t allele of Dnahc8 in the homozygous t haplotype-specific male sterility phenotype (Lyon 1986 Cell 44, 357-363), and the practicable ability of this gene and/or other testis-expressed members of multigene families to affect the evolution of species barriers are discussed.


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