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First published online 8 April 2003
doi: 10.1242/jcs.00430
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Research Article |
1 Section of Molecular and Cell Biology, University of California – Davis,
One Shields Avenue, Davis, CA 95616, USA
2 Department of Cell and Human Anatomy, University of California – Davis,
One Shields Avenue, Davis, CA 95616, USA
3 Department of Social and Environmental Medicine, Osaka University, Suita,
Osaka, Japan
* Author for correspondence (e-mail: pdprimakoff{at}ucdavis.edu)
Accepted 14 February 2003
Glycosylphosphatidylinositol-anchored proteins on the egg surface have been
proposed to play a role in gamete fusion on the basis of in vitro experiments.
We tested this hypothesis by asking if oocyte GPI-anchored proteins are
required for fertilization in vivo. Oocyte-specific knockout mice were created
using the Cre/loxP system to delete a portion of the Pig-a
gene, which encodes an enzyme involved in GPI anchor biosynthesis. Conditional
Pig-a-knockout females are infertile, and eggs recovered from the
females after mating are unfertilized. In in vitro assays, the knockout eggs
are severely deficient in their ability to fuse with sperm. These results
demonstrate that GPI-anchored proteins are required for gamete fusion. Loss of
the GPI-anchored complement of plasma membrane proteins could prevent fusion
by altering the organization and function of GPI-anchored protein-containing
lipid domains. Alternatively, a single GPI-anchored protein may be required in
the fusion process. To distinguish between these possibilities, we have begun
to identify the GPI-anchored proteins on the egg surface. We have identified
one egg GPI-anchored protein as CD55, an 
70 kDa complement regulatory
protein. It has previously been found that CD55-knockout mice are fertile,
demonstrating that CD55 is not essential for fertilization. This finding also
means that the presence of the full complement of egg GPI-anchored proteins is
not necessary for gamete fusion. Other egg GPI-anchored proteins acting in the
fusion process can now be investigated, with the goal of understanding the
mechanism of their function in sperm-egg fusion.
Key words: GPI-anchored protein, Sperm-egg fusion, Fertilization, Cre/loxP, Pig-a, Infertile
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