PARENT SESSION
MINISYMPOSIUM VII. Conditional Gene Disruption in the Mouse: Concepts and Applications.
11:00 AM-12:30 PM
Grand Ballroom V
Chair: Adashi, Eli¹, ¹

(M22) TARGETING OOCYTE-SPECIFIC GENES: THE ZONA PELLUCIDA PARADIGM.

Dean, Jurrien¹, ¹ Laboratory of Cellular and Developmental Biology, NIDDK, Bethesda, MD

ABSTRACT- Gene products expressed in oocytes play important roles in folliculogenesis, fertilization, and pre-implantation development. Using the zona pellucida as a paradigm for better understanding genetic hierarchies unique to mammalian oocytes, we have defined the genes that encode the mouse and human zona proteins (ZP1, ZP2, ZP3) and identified upstream regulators of their expression. One regulator, FIG (Factor in the Germline, alpha), has been shown to bind to the promoters of mouse Zp1, Zp2 and Zp3 genes and transactivate reporter genes in vitro. Mouse lines lacking FIG have been established. Adult males are normal, but females have small ovaries and are infertile. Developing Fig null females have ovaries that are indistinguishable from normal littermates until just prior to birth. Then, despite the presence of granulosa cells, oocytes do not form into primordial follicles and are lost within two days after birth. These data are consistent with FIG regulating one or more genes involved in formation of follicles, without which oocytes are lost and females are infertile. Although eutherian mammals fertilize internally and the zona pellucida is unlikely to serve as a basis of speciation. the order-specific sperm binding to ovulated eggs can be exploited in genetic investigations of the molecular basis of fertilization. Using embryonic stem cell technology and transgenesis, mouse lines lacking either mouse ZP1, ZP2 or ZP3 as well as mouse lines expressing human ZP2 or ZP3 have been established. By crossing the appropriate lines, mice with ′humanized′ zonae can be derived in which the homologous human zona protein replaces the endogenous mouse protein. The phenotypic analysis of mice lacking individual endogenous zona proteins or expressing a replacement human homologue has provided insight into the molecular basis of zona matrix formation and of sperm binding.

KEY WORDS: zona pellucida, oocyte-specific genes, factor in the germline, alpha, fertilization