An axonemal dynein at the Hybrid Sterility 6 locus: implications for t haplotype-specific male sterility and the evolution of species barriers

Poor sperm motility characterized by a distinct aberration in flagellar wav eform known as "curlicue" is a hallmark of t haplotype (t) homozygous male sterility. Previous studies have localized "curlicue" and a flagellar devel opmental defect, "whipless", to the Hybrid Sterility 6 locus (Hst6), betwee n the markers Pim1 and Crya1. More recent heterospecific breeding experimen ts between Mus spretus (Spretus) and Mus musculus domesticus (Domesticus) h ave mapped the primary source(s) of both "curlicue" and "whipless" to a sma ll sub-locus of Hst6 Curlicue a (Ccua). Here we report the complete physica l isolation of the Ccua locus and the identification of a candidate gene fo r expression of both "whipless" and "curlicue" at its proximal end, an axon emal dynein heavy chain gene, Dnahc8, formerly mapped by interspecific back cross analysis near Pim1. Dnahc8 mRNA expression commences in the Domesticu s wild-type testis just prior to flagellar assembly and is testis-specific in the adult male. However, expression of Dnahc8 is not readily evident in the testis of either Spretus or "whipless" animals (Domesticus males homozy gous for the Spretus allele of Dnahc8). Our results argue that Dnahc8 is fu ndamental to flagellar organization and function in Domesticus, but not Spr etus, and suggest that Dnahc8 is integral to both Hst6- and I-specific male infertility.