The large size of the pig and its similarity in anatomy, physiology, metabolism, and genetics to humans make it an ideal platform to develop a genetically defined, large animal model of cancer. To this end, we created a transgenic "oncopig" line encoding Cre recombinase inducible porcine transgenes encoding KRASG12D and TP53R167H, which represent a commonly mutated oncogene and tumor suppressor in human cancers, respectively. Treatment of cells derived from these oncopigs with the adenovirus encoding Cre (AdCre) led to KRASG12D and TP53R167H expression, which rendered the cells transformed in culture and tumorigenic when engrafted into immunocompromised mice. Finally, injection of AdCre directly into these oncopigs led to the rapid and reproducible tumor development of mesenchymal origin. Transgenic animals receiving AdGFP (green fluorescent protein) did not have any tumor mass formation or altered histopathology. This oncopig line could thus serve as a genetically malleable model for potentially a wide spectrum of cancers, while controlling for temporal or spatial genesis, which should prove invaluable to studies previously hampered by the lack of a large animal model of cancer.

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Published in PLOS One, v. 10, no. 7, article e0128864, p. 1-18.

© 2015 Schook et al.

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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This work was supported by the following: China Scholarship Council (CSC): WH; Brazilian Scholarship Program "Science Without Borders" promoted by the National Counsel of Technological and Scientific Development (http://www.iie.org/Programs/Brazil-Scientific-Mobility): FMR, TVC and FKS; American Cancer Society (http://www.cancer.org/research/applyforaresearchgrant/) (ACS178898): YL; American Cancer Society (http://www.cancer.org/research/applyforaresearchgrant/) (ACS178898): CMC; U.S. National Institutes of Health (http://grants.nih.gov/grants/oer.htm) (CA123031) and the Edward Spiegel Fund of the Lymphoma Foundation (http://www.lymphomafoundation.org/): CMC; United States Department of Agriculture (USDA)(http://www.csrees.usda.gov/)(AG 58-5438-2-307), The U.S. National Institutes of Health (http://grants.nih.gov/grants/oer.htm) (CA 153132), the Edward William & Jane Marr Gutgsell Foundation (http://provost.illinois.edu/about/chairs.html), and the Cooperative Research Program for Agriculture Science & Technology Development (http://www.csrees.usda.gov/)(PJ009103); Rural Development Administration, Republic of Korea (http://www.rda.go.kr/foreign/eng/): LBS; and U.S. National Institutes of Health (U42 OD011140): RSP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.