International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)

POSTER 80 - TsgL1 and Tsga2, Two New Candidates at the Hst6 Locus for t Haplotype Effects on Male Fertility

Hui L, Pilder S
Temple University School Of Medicine

The Hst6 locus maps to In(17)4 of the mouse t complex, and contains one or more genes that cause male sterility via deleterious effects on sperm flagellar movement and ultrastructure. While a prime candidate for both effects is an axonemal dynein heavy chain gene, Dnahc8, the genomic region immediately flanking the Dnahc8 locus contains two additional testis-specifically expressed genes, TsgL1 and Tsga2, whose expression characteristics differ significantly between t haplotype (t) and wildtype (+) alleles. Tsga2, located just distal to Dnahc8, is a rather unremarkable gene producing an abundant transcript of ~1-kb with a 906-bp ORF. Expression is reduced in the testes of t homozygotes, and TSGA2t contains 14 amino acid changes, most within the N-terminal two-thirds of the ORF, relative to TSGA2+. In situ hybridization studies indicate that Tsga2 expression is abundant in pachytene spermatocytes, with progressively decreasing levels in round and elongating spermatids (consistent with the previously reported localization of TSGA2 in late spermatocytes and round spermatids). TsgL1, located just proximal to Dnahc8 shows complex organizational and expression patterns. Multiple messages are transcribed from this >350-kb locus, the three smallest (~3.5, ~2.5, and ~1.0-kb) being testis-specific, each consisting of several small exons with enormous introns. In t, the 1.0-kb isoform is not expressed, and preliminary analysis of + and t transcripts suggests that they differ greatly at their 5'- and 3'-ends. In summary, our early results support the candidacy of Tsga2 and TsgL1 for t effects on male fertility, and continued efforts to elucidate their function are underway.

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