Abstract
Oncogenic mutations of KRAS play a major role in human carcinogenesis. Here we describe viable gene-targeted pigs carrying a latent KRAS G12D mutant allele that can be activated by Cre recombination. These have been produced as part of a program to model human cancers in pigs by replicating genetic lesions known to initiate and drive human disease. Cre-activated KRAS G12D animals add to a growing set of gene-targeted pigs that includes a Cre-activated oncogenic mutant TP53, a Cre-responsive dual fluorescent reporter and two truncating mutations of APC (adenomatous polyposis coli). These alleles can be combined and activated in various tissues to produce new models for cancer research.
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Acknowledgments
The authors would like to thank Peggy Müller-Fliedner for excellent technical assistance, Steffen and Viola Loebnitz and Josef Reim for dedicated animal husbandry. Support for this work was provided by the German Research Foundation (DFG) (Grant Number SCHN 971/3-1, WO 685/16-1), and the German Federal Ministry of Education and Research (BMBF) (Grant Number 16EX1024D). The authors are members of COST Action BM1308 ‘Sharing Advances on Large Animal Models’ (SALAAM).
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The authors declare that they have no conflict of interest.
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Shun Li and Marlene Edlinger have contributed equally to this work.
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Li, S., Edlinger, M., Saalfrank, A. et al. Viable pigs with a conditionally-activated oncogenic KRAS mutation. Transgenic Res 24, 509–517 (2015). https://doi.org/10.1007/s11248-015-9866-8
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DOI: https://doi.org/10.1007/s11248-015-9866-8