Mfsd14a (Hiat1) gene disruption causes globozoospermia and infertility in male mice.

The Mfsd14a gene, previously called Hiat1, encodes a transmembrane protein of unknown function with homology to the solute carrier protein family. To study the function of the MFSD14A protein, mutant mice (Mus musculus, strain 129S6Sv/Ev) were generated with the Mfsd14a gene disrupted with a LacZ reporter gene. Homozygous mutant mice are viable and healthy, but males are sterile due to a 100-fold reduction in the number of spermatozoa in the vas deferens.

Gpr54-/- mice show more pronounced defects in spermatogenesis than Kiss1-/- mice and improved spermatogenesis with age when exposed to dietary phytoestrogens.

Mice with mutations in the kisspeptin signaling pathway (Kiss1(-/-) or Gpr54(-/-)) have low gonadotrophic hormone levels, small testes, and impaired spermatogenesis. Between 2 and 7 months of age, however, the testes of the mutant mice increase in weight and in Gpr54(-/-) mice, the number of seminiferous tubules containing spermatids/spermatozoa increases from 17 to 78%. In contrast, the Kiss1(-/-) mice have a less severe defect in spermatogenesis and larger testes than Gpr54(-/-) mice at both 2 and 7 months of age.