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Disease models

Recombination activating gene 2 (RAG2) knockout pigs to model immunodeficiency and evaluate transplant-based therapies

Pigs with RAG2 knocked out could be useful as models of human immunodeficiencies and for testing transplant-based therapies. In vitro, engineered transcription activator-like effector nucleases (TALENs) were used to knock out RAG2 in pig fibroblasts, which were then used in a somatic cell nuclear transfer procedure to generate eight RAG2 knockout pigs. The RAG2 knockout pigs failed to gain weight and showed a severe combined immunodeficiency phenotype that resulted in death or euthanasia before 29 days. A subsequent cohort of RAG2 knockout pigs housed in cleaner conditions remained healthy for eight weeks and rapidly developed teratomas when injected with human induced pluripotent stem (iPS) cells. Next steps could include using the pigs to evaluate transplantation of stem cell-derived tissues.

SciBX 7(22); doi:10.1038/scibx.2014.656
Published online June 5, 2014

Unpatented; pigs available from the National Swine Resource and Research Center at the University of Missouri

Lee, K. et al. Proc. Natl. Acad. Sci. USA; published online May 5, 2014;
Contact: Jin-Hoi Kim, Konkuk University, Seoul, South Korea
Contact: Randall S. Prather, University of Missouri, Columbia, Mo.
Contact: R. Michael Roberts, same affiliation as above