Transgenic models in the study of reproduction

The development of techniques to manipulate genes within mouse embryonic stem (ES) cells has allowed investigators to study the functions of many genes in vivo. We have used these techniques to functionally mutate genes to study how the loss of the gene affects development, oncogenesis, and reproduction. Genes affecting development include members of the transforming growth factor-beta (TGF-beta) superfamily and their signaling pathway. We have shown that mutations in this complicated signaling network affect a wide range of embryonic developmental processes including craniofacial morphogenesis, dentition and muscle development. One specific member of TGF-beta family, inhibin alpha, has been identified as a novel tumor suppressor in the testes, ovaries, and adrenal glands. Another focus of research in the laboratory is the analysis of roles of proteins in the hypothalamic-pituitary-gonadal axis and the affect of disrupting this pathway on reproductive function. We have demonstrated that several genes expressed in the pituitary and gonads are required for folliculogenesis leading to female infertility and in two cases are important for Sertoli cell proliferation in males. The studies using ES cell technology has enabled us to dissect two complex networks in animal models.