Haplo-deficiency of ODF1/HSPB10 in mouse sperm causes relaxation of head-to-tail linkage.

The small heat shock protein ODF1/HSPB10 is essential for male fertility in mice. Targeted deletion of Odf1 resulted in acephalic sperm in homozygous mice of mixed background (C57BL/6J//129/Sv), whereas heterozygous animals are fully fertile. To further elucidate the function of ODF1, we generated incipient congenic mice with targeted deletion of Odf1 by successive backcrossing on the 129/Sv background. We observed that fecundity of heterozygous Odf1(+/-) male mice was severely reduced over backcross generations. However, neither aberrant sperm parameters nor sperm anomalies could be observed. Ultra-structural analyses of sperm from incipient congenic heterozygous Odf1(+/-) males of backcross generation N7 revealed no obvious pathological findings. However, we observed an enlargement of the distance between nuclear membrane and capitulum, indicating a weakening of the sperm head-to-tail coupling. Severe male subfertility provoked by haplo-deficiency of ODF1 is therefore most probably caused by impaired head-to-tail coupling that eventually might induce sperm decapitation on the specific conditions of in vivo fertilisation. As subfertility in haplo-deficient ODF1 male mice could not be diagnosed by semen analysis, it seems to be a paradigm for unexplained infertility that is a frequent diagnosis for male fertility impairment in humans.