Spermatogonial Stem Cells in the Rat and Mouse

An ability to culture and genetically manipulate spermatogonial stem cells could lead to direct germ line transmission of modified genomes, methods to correct male infertility, and means to rapidly screen for germ cell directed contraceptive. Although most genetic models revolve around the mouse, principally because of their ability to maintain pluripotency of embryonic stem (ES) cells in culture, the laboratory rat is one of the most comprehensively studied mammals. In the absence of pluripotent ES cells, an alternative would be germ line transmission through the targeting of male germ cells in culture, followed by testicular transplantation, colonization, and subsequent production of genetically modified mature spermatozoa for fertilization. A second and similar approach is to genetically modify male germ cells in culture and induce differentiation to spermatids followed by the production of genetically modified pups through egg intracytoplasmic injection. The only established method to deliver transgenes directly into the male germ line is through retroviral-mediated gene delivery into spermatogonial stem cells. The identification of molecular markers for the spermatogonial stem cell would accelerate the development of such technology. Molecular markers for spermatogonial stem cells have now been identified, but whether some or many of these transcripts are essential for stem cell maintenance is not known.