SPERM FROM BETA-1,4-GALACTOSYLTRANSFERASE-NULL MICE ARE REFRACTORY TOZP3-INDUCED ACROSOME REACTIONS AND PENETRATE THE ZONA-PELLUCIDA POORLY

A variety of sperm surface components have been suggested to mediate g amete recognition by binding to glycoside ligands on the egg coat glyc oprotein ZP3. The function of each of these candidate receptors is bas ed upon varying degrees of circumstantial and direct evidence: however , the effects on fertilization of targeted mutations in any of these c andidate receptors have not yet been reported, In this paper, we descr ibe the effects of targeted mutations in beta 1,4-galactosyltransferas e, the best studied of the candidate receptors for ZP3. Surprisingly, galactosyltransferase-null (gt(-/-)) males are fertile; however, sperm from gt(-/-) males bind less radiolabeled ZP3 than wild-type sperm, a nd are unable to undergo the acrosome reaction in response to either Z P3 or anti-galactosyltransferase antibodies, as do wild-type sperm, In contrast, gt(-/-) sperm undergo the acrosome reaction normally in res ponse to calcium ionophore, which bypasses the requirement for ZP3 bin ding, The inability of gt(-/-) sperm to undergo a ZP3-induced acrosome reaction renders them physiologically inferior to wild-type sperm, as assayed by their relative inability to penetrate the egg coat and fer tilize the oocyte in vitro, Thus, although ZP3 binding and subsequent induction of the acrosome reaction are dispensable for fertilization, they impart a physiological advantage to the fertilizing sperm, A seco nd strain of mice was created that is characterized by a loss of of th e long galactosyltransferase isoform responsible for ZP3-dependent sig nal transduction, but which maintains normal levels of Golgi galactosy lation, Sperm from these mice show that the defective sperm-egg intera ctions in gt(-/-) mice are due directly to a loss of the long galactos yltransferase isoform from the sperm surface and are independent of th e state of intracellular galactosylation during spermatogenesis.