Developmental Biology

PI 3-Kinase Requirement for Male Fertility

Science's STKE  08 Feb 2000:
Vol. 2000, Issue 18, pp. tw6
DOI: 10.1126/stke.2000.18.tw6

The c-kit gene encodes a transmembrane tyrosine kinase receptor that activates several signaling pathways and is essential for hematopoiesis, melanogenesis, and gametogenesis. However, the various roles of these pathways in development is not well understood. Blume-Jensen et al. "knocked in" a kinase-competent c-kit point mutant (Y to F 719) into mice that fails to associate with phosphatidylinositol 3-kinase (PI 3-kinase). The homozygous mice were viable, and exhibited no hematopoietic or melanogenic defects. The male mice, however, were sterile, whereas the female mice were fertile. Mutant male pups were defective for spermatogonial stem-cell differentiation and exhibited reduced germ-cell proliferation. Therefore, the Kit-dependent activation of PI 3-kinase appears necessary for male germ cell differentiation and fertility in male mice.

Blume-Jensen, P., Jiang, G., Hyman, R., Lee, K.-F., O'Gorman, S., and Hunter, T. (2000) Kit/Stem cell factor receptor-induced activation of phosphatidylinositol 3-kinase is essential for male fertility. Nature Gene. 24: 157-162. [Online Journal]