| Literature DB >> 19628861 |
Aron M Geurts1, Gregory J Cost, Yevgeniy Freyvert, Bryan Zeitler, Jeffrey C Miller, Vivian M Choi, Shirin S Jenkins, Adam Wood, Xiaoxia Cui, Xiangdong Meng, Anna Vincent, Stephen Lam, Mieczyslaw Michalkiewicz, Rebecca Schilling, Jamie Foeckler, Shawn Kalloway, Hartmut Weiler, Séverine Ménoret, Ignacio Anegon, Gregory D Davis, Lei Zhang, Edward J Rebar, Philip D Gregory, Fyodor D Urnov, Howard J Jacob, Roland Buelow.
Abstract
The toolbox of rat genetics currently lacks the ability to introduce site-directed, heritable mutations into the genome to create knockout animals. By using engineered zinc-finger nucleases (ZFNs) designed to target an integrated reporter and two endogenous rat genes, Immunoglobulin M (IgM) and Rab38, we demonstrate that a single injection of DNA or messenger RNA encoding ZFNs into the one-cell rat embryo leads to a high frequency of animals carrying 25 to 100% disruption at the target locus. These mutations are faithfully and efficiently transmitted through the germline. Our data demonstrate the feasibility of targeted gene disruption in multiple rat strains within 4 months time, paving the way to a humanized monoclonal antibody platform and additional human disease models.Entities:
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Year: 2009 PMID： 19628861 PMCID： PMC2831805 DOI： 10.1126/science.1172447
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728