SPERMATOZOA LACKING ACROSIN PROTEIN SHOW DELAYED FERTILIZATION

Acrosin (ACR), a serine proteinase located in the acrosome of the sper m, has been presumed to be involved in the recognition and binding of the sperm to the zona pellucida of the ovum and the sperm penetration through the zona pellucida. To examine the function of acrosin in vivo , we have generated mice carrying a mutation at the acrosin locus (Acr ) through targeted disruption in embryonic stem (ES) cells. One chimer ic male and female transmitted the targeted gene through their germ li ne. Homozygous Acr(-/-) mice ave fertile and yield litters comparable in number and size to those of Acr(+/+) mice. These data show that spe rm of the homozygous Acr(-/-) mice are able to penetrate the zona pell ucida, fertilize the ovum, and produce viable offspring. However, sper matozoa lacking acrosin protein show a delayed fertilization. One chim eric male which contained the targeted gene in 20% of its sperm transm itted only the Acr(+) allele to its progeny. Furthermore, in vitro fer tilization with equally mixed sperm cells of Acr(+/+) and Acr(-/-) mic e resulted in fertilization only with the Acr(+) sperm cells. Incubati on of oocytes with Acr(+) or Acr(-) sperm show that the Acr(+) sperm a re faster to fertilize the oocytes than the Acr(-) sperm cells. These results suggest that Acr(-) sperm have a selective disadvantage when t hey are in competition with Acr(+) sperm. (C) 1997 Wiley-Liss, Inc.