Researchers at the University of Pennsylvania School of Veterinary Medicine have demonstrated the potential of a new strategy for genetic modification of large animals. The method employs a harmless gene therapy virus that transfers a genetic modification to male reproductive cells, which is then passed naturally on to offspring.
Ina Dobrinski, associate professor and director of the Center for Animal Transgenesis and Germ Cell Research at Penn Vet, and her colleagues introduced adeno-associated virus, AAV, to male germline stem cells in both goats and mice. The study showed that AAV stably transduced male germ line stem cells and led to transgene transmission through the male germ line.
The findings, available online in The FASEB Journal and in the February 2008 print edition, are the first report of transgenesis via germ cell transplantation in a non-rodent species, a promising approach to germ line genetic modification. It also demonstrates that germline transduction and germ cell transplantation in large animals provides an approach that is potentially less costly than microinjection and cloning, the traditional methods used to generate transgenic large animal models for biomedical research.
Researchers used mouse germ cells harvested from experimentally induced cryptorchid donor testes that were then exposed in vitro to AAV vectors carrying a green fluorescent protein transgene and transplanted to germ cell-depleted recipient testes, resulting in colonization of the recipient testes by transgenic donor cells.
When researchers mated these recipient males with wild-type females, 10 percent of offspring carried the gene originally introduced into the transplanted germ cells, meaning the genetic modification had been passed on. To broaden the approach to non-rodent species, AAV-transduced germ cells from goats were transplanted to recipient males in which endogenous germ cells had been depleted by fractionated testicular
|Contact: Jordan Reese|
University of Pennsylvania