PT - JOURNAL ARTICLE AU - Geurts, Aron M. AU - Cost, Gregory J. AU - Freyvert, Yevgeniy AU - Zeitler, Bryan AU - Miller, Jeffrey C. AU - Choi, Vivian M. AU - Jenkins, Shirin S. AU - Wood, Adam AU - Cui, Xiaoxia AU - Meng, Xiangdong AU - Vincent, Anna AU - Lam, Stephen AU - Michalkiewicz, Mieczyslaw AU - Schilling, Rebecca AU - Foeckler, Jamie AU - Kalloway, Shawn AU - Weiler, Hartmut AU - Ménoret, Séverine AU - Anegon, Ignacio AU - Davis, Gregory D. AU - Zhang, Lei AU - Rebar, Edward J. AU - Gregory, Philip D. AU - Urnov, Fyodor D. AU - Jacob, Howard J. AU - Buelow, Roland TI - Knockout Rats via Embryo Microinjection of Zinc-Finger Nucleases AID - 10.1126/science.1172447 DP - 2009 Jul 24 TA - Science PG - 433--433 VI - 325 IP - 5939 4099 - http://science.sciencemag.org/content/325/5939/433.short 4100 - http://science.sciencemag.org/content/325/5939/433.full SO - Science2009 Jul 24; 325 AB - 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.