Honaramooz Ali, Behboodi Esmail, Megee Susan O, Overton Susan A, Galantino-Homer Hannah, Echelard Yann, Dobrinski Ina
Center for Animal Transgenesis and Germ Cell Research, Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania 19348, USA.
Biol Reprod. 2003 Oct;69(4):1260-4. doi: 10.1095/biolreprod.103.018788. Epub 2003 Jun 11.
Transplantation of spermatogonial stem cells into syngeneic or immunosuppressed recipient mice or rats can result in donor-derived spermatogenesis and fertility. Recently, this approach has been employed to introduce a transgene into the male germline. Germ-cell transplantation in species other than laboratory rodents, if successful, holds great promise as an alternative to the inefficient methods currently available to generate transgenic farm animals that can produce therapeutic proteins in their milk or provide organs for transplantation to humans. To explore whether germ-cell transplantation could result in donor-derived spermatogenesis and fertility in immunocompetent recipient goats, testis cells were transplanted from transgenic donor goats carrying a human alpha-1 antitrypsin expression construct to the testes of sexually immature wild-type recipient goats. After puberty, sperm carrying the donor-derived transgene were detected in the ejaculates of two out of five recipients. Mating of one recipient resulted in 15 offspring, one of which was transgenic for the donor-derived transgene. This is the first report of donor cell-derived sperm production and transmission of the donor haplotype to the next generation after germ-cell transplantation in a nonrodent species. Furthermore, these results indicate that successful germ-cell transplantation is feasible between immunocompetent, unrelated animals. In the future, transplantation of genetically modified germ cells may provide a more efficient alternative for production of transgenic domestic animals.
将精原干细胞移植到同基因或免疫抑制的受体小鼠或大鼠体内，可导致供体来源的精子发生和生育能力。最近，这种方法已被用于将转基因引入雄性生殖系。在实验室啮齿动物以外的物种中进行生殖细胞移植，如果成功，有望成为目前用于生产能在乳汁中产生治疗性蛋白质或为人类提供移植器官的转基因农场动物的低效方法的替代方案。为了探究生殖细胞移植是否能在具有免疫能力的受体山羊中导致供体来源的精子发生和生育能力，将携带人α-1抗胰蛋白酶表达构建体的转基因供体山羊的睾丸细胞移植到性未成熟的野生型受体山羊的睾丸中。青春期后，在五只受体中的两只的精液中检测到携带供体来源转基因的精子。其中一只受体交配后产生了15只后代，其中一只携带供体来源的转基因。这是关于非啮齿动物物种生殖细胞移植后供体细胞来源的精子产生以及供体单倍型向下一代传递的首次报道。此外，这些结果表明，在具有免疫能力、不相关的动物之间成功进行生殖细胞移植是可行的。未来，转基因生殖细胞的移植可能为转基因家畜的生产提供一种更有效的替代方法。
