TARGETED DISRUPTION OF THE MZP3 GENE RESULTS IN PRODUCTION OF EGGS LACKING A ZONA-PELLUCIDA AND INFERTILITY IN FEMALE MICE

Mammalian eggs are surrounded by a thick extracellular coat, the zona pellucida, that plays important roles during early development. The mo use egg zona pellucida is constructed of three glycoproteins, called m ZP1, mZP2, and mZP3. The gene encoding mZP3 is expressed only by growi ng oocytes during a 2- to 3-week period of oogenesis. Here, the mZP3 g ene was disrupted by targeted mutagenesis using homologous recombinati on in mouse embryonic stem cells. Viable female mice homozygous for th e mutated mZP3 allele (mZP3(-/-)) were obtained. These mice are indist inguishable in appearance from wild-type (mZP3(+/+)) and heterozygous (mZP3(+/-)) littermates. However, although ovaries of juvenile and adu lt mZP3(-/-) females possess growing and fully grown oocytes, the oocy tes completely lack a zona pellucida. Consistent with this observation , eggs recovered from oviducts of superovulated, adult mZP3(-/-) femal es also lack a zona pellucida. Thus far, mZP3(-/-) females mated with wild-type males have failed to become pregnant.