The long-term objective of this project is to improve the treatment and prevention of human infertility. Infertility in the female caused by premature ovarian failure will only be prevented by improving our knowledge of the molecular mechanisms that regulate function of the ovary. This project will determine if AP-2 gamma is critical for the maintenance of female germ line stem cells. Germ line stem cells have just recently been discovered in the mouse ovary, creating a new frontier in reproductive biology. Until this discovery, it had long been believed that females were born with a finite number of oocytes determined prior to birth. The number of potential oocytes a female had at birth was believed to be around 300,000 and that was her lifelong total. The discovery of germline stem cells suggests that new follicles are being produced with new oocytes generated from a stem cell population that continues past birth into adult life. The failure of ovaries to produce germline stem cells could prove to be a leading cause of premature ovarian failure. This proposal will investigate the role of AP-2 gamma in the regulation of germ line stem cells by producing mouse ovaries with mutations to the AP-2 gamma gene. These mutations will be produced utilizing the Cre/loxP gene recombination system. The number of germline stem cells in the ovary will be determined by identifying these cells using germline stem cell markers. The role for AP-2 gamma in sustaining the population of germline stem cells will be verified if fewer cells are detected in the mutant ovaries compared to control. Improving our understanding of the molecular mechanisms that drive the re-population of adult ovaries with oocytes derived from germ line stem cells will lead to possible preventions for premature ovarian failure. The potential for developing successful treatments for human infertility provided by these experiments emphasizes the immediate importance for this research.