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Ovarian development in mice bearing homozygous or heterozygous null
mutations in zona pellucida glycoprotein gene mZP3
P.M. Wassarman1, C. Liu2, J. Chen3, H. Qi1 and E.S. Litscher1
1Department of Cell Biology and Anatomy, Mount Sinai School
of Medicine, NY, 2Columbia-Presbyterian Cancer Center, Columbia University,
College of Physicians and Surgeons, New York and 3Parexel International,
Waltham, MA, USA
Offprint requests to: Dr. Paul
Wassarman, Department of Cell Biology and AnatomyMount Sinai School of Medicine,
One Gustave L. Levy Place, New York, NY 10029-6574, USA
Summary. The plasma membrane
of all mammalian eggs is surrounded by a thick extracellular coat, the zona
pellucida (ZP), whose paramount function is to regulate species-specific
fertilization. The mouse egg ZP is composed of only three glycoproteins,
mZP1-3, that are synthesized and secreted exclusively by oocytes during
their 2-3 week growth phase. Disruption of the mZP3 gene by targeted mutagenesis
in embryonic stem (ES) cells yields mice heterozygous (mZP3+/-) or homozygous
(mZP3-/-) for the null mutation. As expected, male mice bearing the null
mutation are indistinguishable from wild-type males with respect to viability
and fertility. Female mZP3+/- mice are as fertile as wild-type animals,
but their eggs have a thin ZP (~2.7 µm thick) as compared to the ZP
(~6.2 µm thick) of eggs from wild-type animals. On the other hand,
female mZP3-/- mice are infertile and their eggs lack a ZP. The infertility
apparently is due to the lack of a sufficient number of eggs in oviducts
of superovulated mZP3-/- females. Light micrographs reveal that development
of ovarian follicles is often retarded in mZP3-/- mice as compared to wild-type
animals. This is manifested as reduced ovarian weights, reduced numbers
of Graafian follicles, and reduced numbers of fully-grown oocytes in mZP3-/-
females. It seems likely that the pleiotropic effects of the homozygous
null mutation on ovarian development may be due, at least in part, to disruption
of intercellular communication between growing oocytes and their surrounding
follicle cells. Histol Histopathol 13, 293-300 (1998)
Key words: Fertilization, Zona
pellucida, Null mutation, Mouse
DOI: 10.14670/HH-13.293
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