Transgenic mouse models to study follicle-stimulating hormone receptor (FSHR) function in reproduction

Follicle-stimulating hormone (FSH) binds to G protein-coupled FSH receptors (FSHR) expressed on ovarian granulosa cells in low abundance. Activation of FSHR leads to granulosa cell proliferation, differentiation and estrogen production. These events are essential for female fertility.  FSHR signaling pathway is highly conserved between mice and humans. Inactivating mutations in FSHR-encoding gene in mice (Fshr -/-) or women result in ovarian folliculogenesis arrest and female infertility. High affinity and highly potent human FSHR-specific single-domain antibody fragments (SDAb) will be tested in a humanized mouse model with ovary-targeted expression of human FSHR transgene on a Fshr null genetic background. This model permits evaluation of several reproducitve outcomes and may prove as an essential in vivo genetic tool to study FSHR-mediated signaling in ovarian granulosa cells.