The Application of Gene Ablation and Related Technologies to the Study of Ovarian Function

This chapter reviews the models that have helped researchers piece together the molecular mechanisms important for female fertility, from those that mediate primordial germ cell survival to those that conduct oocyte and somatic cell functions during folliculogenesis. It also considers post-ovulatory events contingent on genes expressed in oocytes while still within the ovary. The ability to engineer targeted mutations of the mammalian genome is revolutionizing the ways for studying essential gene functions and has already greatly enhanced the understanding of ovarian development and physiology. When this approach is used to generate a non- functional or null allele, it is termed gene ablation or gene "knockout" technology. Knockout mouse models are being created at an ever-increasing rate, and more than 200 have been reported to date with reproductive phenotypes. This number already surpasses the quantity of naturally occurring mutations associated with identified genes. Embryonic stem (ES) cells, derived from the inner cell mass of mouse blastocysts, can be maintained for long periods in pluripotent states in vitro and altered by targeted mutagenesis. Deleting or altering a particular site in the murine genome relies on the endogenous ES cell homologous recombination machinery to mediate crossover exchanges between the locus to be targeted.