t haplotypes in the mouse compromise sperm flagellar function.

The t haplotypes are variant forms of the proximal portion of chromosome 17 in the mouse. The t haplotypes alter spermatogenesis and many also contain lethal factors. Although the lethal factors vary between t haplotypes, all t haplotypes have the same effect on sperm, that of altering sperm function in fertilization. It is not clear, however, whether the nature of the sperm dysfunction is the same in all t haplotypes. Studies to date have focused on only one or two aspects of sperm function or have not examined sperm from males carrying different t haplotypes. In addition, factors within the t haplotypes interact with the genetic background, so that comparisons to sperm from t/+ or +/+ mice having different alleles at loci outside the t haplotypes may not be valid. To determine the nature of the sperm dysfunction caused by the t haplotypes, we have studied sperm from mice of the same genetic strain carrying none, one, or two t haplotypes. Sperm from tw32/+, tw5/+, and tw32/tw5 mice exhibited premature hyperactivation, a type of vigorous but nonprogressive motility correlated with fertility, while their rates of capacitation (the ability to undergo the acrosome reaction in response to zona proteins) and spontaneous acrosome reaction were similar to those of wild-type sperm. In addition, sperm flagellar curvature was abnormal: flagella from heterozygotes had an acute bend in the midpiece, giving the sperm a "fishhook" appearance, while the entire flagellum of sperm from tw32/tw5 mice was curled. Also, fewer sperm from tw32/tw5 mice were initially motile. Since all of these motility defects were dependent on exogenous calcium, the t haplotypes could specify an abnormal, calcium-sensitive component of the flagellum. The motility defects could also contribute to the dysfunction of these sperm by inhibiting their passage to the site of fertilization in vivo.