Role of Skp2 in Ovarian Development and its Effects on Granulosa Cells
Progression of the cell cycle is highly regulated by a series of complex molecules that enable the cell to undergo proliferation and division and is obligatory for normal ovarian function in females. p27Kip1 has been suggested to play an important role in the regulation of the cell cycle. Loss of p27Kip1 has been shown to lengthen a cell's proliferation period, which leads to an increase in body size and multiple organ hyperplasia in mice. Another cell cycle regulator, Skp2, plays an important role in the cell cycle as well. The function of Skp2 in cell cycle is to regulate ubiquitination and breakdown of p27Kip1, and thus regulates p27Kip1 concentration in the cell. Loss of Skp2 leads to a significant reduction in the body size. It has been reported that mice lacking Skp2, in contrast to p27Kip1, are fertile. Lack of p27Kip1 results in a noticeable increase ovarian size, but in contrast, mice lacking Skp2 have a reduced ovarian size. In addition, ovaries of p27Kip1 - / - / Skp2 - / - mice have not yet been examined. Here we compare overall development of the ovary and granulosa cells in wild type, Skp2 KO, p27Kip1 KO and Skp2/ p27Kip1 KO mice using immunohistochemistry, hematoxylin and eosin staining. With this approach we can identify the role of Skp2, with or without the absence of p27Kip1, in development of the ovary and granulosa cells. As hypothesized, Skp2 regulates ovarian size and granulosa cell proliferation and the defect is partially, but not entirely, mediated by the regulation of p27Kip1.
School:
University of Puerto Rico at Bayamón
Department:
General Biology
Research Advisor:
Paul S. Cooke
Department of Research Advisor:
Veterinary Biosciences
Year of Publication:
2005