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Adeno‐associated virus (AAV)‐mediated transduction of male germ line stem cells results in transgene transmission after germ cell transplantation
Author(s) -
Honaramooz Ali,
Megee Susan,
Zeng Wenxian,
Destrempes Margret M.,
Overton Susan A.,
Luo Jinping,
Galantino-Homer Hannah,
Modelski Mark,
Chen Fangping,
Blash Stephen,
Melican David T.,
Gavin William G.,
Ayres Sandra,
Yang Fang,
Wang P. Jeremy,
Echelard Yann,
Dobrinski Ina
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.07-8935com
Subject(s) - transgene , germ cell , biology , transduction (biophysics) , transgenesis , germline , stem cell , transplantation , microbiology and biotechnology , genetically modified mouse , embryo , andrology , immunology , gene , genetics , medicine , embryogenesis , reproductive technology , biochemistry
ABSTRACT We explored whether exposure of mammalian germ line stem cells to adeno‐associated virus (AAV), a gene therapy vector, would lead to stable transduction and transgene transmission. Mouse germ cells harvested from experimentally induced cryptorchid donor testes were exposed in vitro to AAV vectors carrying a GFP transgene and transplanted to germ cell‐depleted syngeneic recipient testes, resulting in colonization of the recipient testes by transgenic donor cells. Mating of recipient males to wild‐type females yielded 10% transgenic offspring. To broaden the approach to nonrodent species, AAV‐transduced germ cells from goats were transplanted to recipient males in which endogenous germ cells had been depleted by fractionated testicular irradiation. Transgenic germ cells colonized recipient testes and produced transgenic sperm. When semen was used for in vitro fertilization (IVF), 10% of embryos were transgenic. Here, we report for the first time that AAV‐mediated transduction of mammalian germ cells leads to transmission of the transgene through the male germ line. Equally important, this is also the first report of transgenesis via germ cell transplantation in a nonrodent species, a promising approach to generate transgenic large animal models for biomedical research.—Honaramooz, A., Megee, S., Zeng, W., Destrempes, M.M., Overton, S.A., Luo, J., Galantino‐Homer, H., Modelski, M., Chen, F., Blash, S., Melican, D. T., Gavin, W. G., Ayres, S., Yang, F., Wang, P. J., Echelard, Y., Dobrinski, I. Adeno‐associated virus (AAV) ‐mediated transduction of male germ line stem cells results in transgene transmission after germ cell transplantation. FASEB J. 22, 374–382 (2008)