Germ cell transplantation - a novel approach to 'designer' animals?

Abstract

AbstractTransplantation of male germ line stem cells from fertile donor mice to the testes of infertile recipient mice results in donor-derived spermatogenesis and transmission of the donor's genetic material to the offspring of recipient animals. Although most widely used in rodents, germ cell transplantation has been applied to pigs, goats and cattle, as well as primates. In large mammals, germ cells can be transplanted to a recipient testis using ultrasound guidance. Importantly, germ cell transplantation was successful between unrelated, immuno-competent donors and recipients in livestock species, whereas transplantation in rodents requires genetically matched or immuno-compromized recipients. Efficiency of colonization of the recipient testis by donor-derived germ cells can be improved by pretreatment of the recipient animal to deplete endogenous germ cells. Genetic manipulation of germ line stem cells before transplantation will result in the production of transgenic sperm. Transgenesis through the male germ line has tremendous potential in livestock species where embryonic stem cell technology is not available and current options to generate transgenic animals are inefficient. Introduction of a genetic change prior to fertilization will circumvent problems associated with manipulation of early embryos and developmental abnormalities associated with somatic cell nuclear transfer and reprogramming. Current research is directed toward improving isolation and culture of male germ line stem cells from livestock species to increase efficiency of transgene transmission and to allow for gene targeting prior to germ cell transplantation. Germ cell transplantation then represents an approach to germ line manipulation through use of transgenic sperm for natural breeding that is potentially more efficient than currently existing strategies.