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Science 292 (5518): 920-923

Copyright © 2001 by the American Association for the Advancement of Science

Requirement of Phospholipase C&dgr;4 for the Zona Pellucida-Induced Acrosome Reaction

Kiyoko Fukami,1* Kazuki Nakao,2 Takafumi Inoue,3 Yuki Kataoka,4 Manabu Kurokawa,5 Rafael A. Fissore,5 Kenji Nakamura,2 Motoya Katsuki,2 Katsuhiko Mikoshiba,36 Nobuaki Yoshida,4 Tadaomi Takenawa1

Several phospholipase C (PLC) isoforms have been found in male and female mammalian gametes, and splicing isoforms of PLCdelta 4 are predominantly expressed in testis. Here we report that male mice in which the PLCdelta 4 gene had been disrupted either produced few small litters or were sterile. In vitro fertilization studies showed that insemination with PLCdelta 4-/- sperm resulted in significantly fewer eggs becoming activated and that the calcium transients associated with fertilization were absent or delayed. PLCdelta 4-/- sperm were unable to initiate the acrosome reaction, an exocytotic event required for fertilization and induced by interaction with the egg coat, the zona pellucida. These data demonstrate that PLCdelta 4 functions in the acrosome reaction that is induced by the zona pellucida during mammalian fertilization.

1 Department of Biochemistry,
2 Division of DNA Biology and Embryo Engineering, Center for Experimental Medicine,
3 Department of Neurobiology,
4 Division of Gene Expression and Regulation, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8039, Japan.
5 Department of Veterinary and Animal Sciences, Paige Laboratory, University of Massachusetts, Amherst, MA 01003, USA.
6 Brain Science Institute, Riken, Hirosawa, Wako, Saitama 351-0198, Japan.
*   To whom correspondence should be addressed. E-mail: kfukami{at}

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