Selective expression of KrasG12D in granulosa cells of the mouse ovary causes defects in follicle development and ovulation.

ABSTRACT: Activation of the RAS family of small G-proteins is essential for follicle stimulating hormone-induced signaling events and the regulation of target genes in cultured granulosa cells. To analyze the functions of RAS protein in granulosa cells during ovarian follicular development in vivo, we generated conditional knock-in mouse models in which the granulosa cells express a constitutively active KrasG12D. The KrasG12D mutant mice were subfertile and exhibited signs of premature ovarian failure. The mutant ovaries contained numerous abnormal follicle-like structures that were devoid of mitotic and apoptotic cells and cells expressing granulosa cell-specific marker genes. Follicles that proceeded to the antral stage failed to ovulate and expressed reduced levels of ovulation-related genes. Th

SUBMITTER: Fan HY 

PROVIDER: S-EPMC3541831 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature