Resumen de Ovarian development in mice bearing homozygous or heterozygous null mutations in zona pellucida glycoprotein gene mZP3

P. M. Wassarman, C. Liu, J. Chen, H. Qi, E. S. Litscher

• The plasma membrane of all mammalian eggs is surrounded by a thick extracellular coat, the zona pellucida (ZP), whose paramount function is to regulate speci es-specific fertilization. The mouse egg ZP is composed of only three glycoproteins, mZP 1-3, that are synthesized and secreted exclusively by oocytes during their 2-3 week growth phase. Disruption of the mZP 3 gen e by targeted mutagenesis in embryonic stem (ES) cells yields mice heterozygous (mZP3+1-) or homozygous (mZP3-1-) 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 mZP 3+1- mice are as fertile as wild-type animals, but their eggs have a thin ZP (~2 7 I'm thick) as compared to the ZP (~6.2l1m thick) of eggs from wild-type animals. On the other hand , female /IIZP 3-1- 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 mZP3-1- females. Light micrographs reveal that development of ovarian follicles is often retarded in mZP 3-1- 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 mZP3-1- females. It seems likely that the pleiotropic effects of the homozygou s null mutation on ovarian development may be due, at least in patt, to disruption of intercellular communication between growing oocytes and their surrounding follicle cells.