To elucidate the role of the mouse geneTcte3(Tctex2), which encodes a putative light chain of the outer dynein arm of cilia and sperm flagella, we have inactivated this gene in mice using targeted disruption. Breeding of heterozygous males and females resulted in normal litter size; however, we were not able to detect homozygousTcte3-deficent mice using standard genotype techniques. In fact, our results indicate the presence of at least three highly similar copies of theTcte3gene (Tcte3-1,Tcte3-2, andTcte3-3) in the murine genome. Therefore, quantitative real-time PCR was established to differentiate between mice having one or two targetedTcte3-3alleles. By this approach,Tcte3-3−/−animals were identified, which were viable and revealed no obvious malformation. Interestingly, some homozygousTcte3-3-deficient male mice bred with wild-type female produced no offspring while otherTcte3-3-deficient males revealed decreased sperm motility but were fertile. In infertileTcte3-3−/−males, spermatogenesis was affected and sperm motility was reduced, too, resulting in decreased ability of Tcte3-3-deficient spermatozoa to move from the uterus into the oviduct. Impaired flagellar motility is not correlated with any gross defects in the axonemal structure, since outer dynein arms are detectable in sperm ofTcte3-3−/−males. However, in infertile males, deficientTcte3-3function is correlated with increased apoptosis during male germ cell development, resulting in a reduction of sperm number. Moreover, multiple malformations in developing haploid germ cells are present. Our results support a role ofTcte3-3in generation of sperm motility as well as in male germ cell differentiation.
Cytoplasmic dynein (ddlc1) mutations cause morphogenetic defects and apoptotic cell death in Drosophila melanogaster.