Embryonic stem (ES) cells are powerful tools for generating genetically modified animals that can assist in advancing our knowledge of mammalian physiology and disease. Pigs provide outstanding models of human genetic diseases due to the striking similarities to human anatomy, physiology and genetics, but progress with porcine genetic engineering has been hampered by the lack of germline-competent pig ES cells. To overcome this limitation, genetically modified pigs have been produced using genetically modified somatic cells and nuclear transfer (NT). Yet, somatic cells exhibit limited proliferative capacity and have an extremely low frequency of homologous recombination compared to ES cells. Hence, only a few knockout pig models have been reported thus far using standard gene-targeting approaches.

Remarkably, induced pluripotent stem cells (iPSCs) have been generated by reprogramming somatic cells from multiple mammalian species using defined cocktails of transcription factors1. Mouse iPSCs have passed the crucial test of germline contribution and generation of all-iPSC mice through tetraploid embryo complementation2. This demonstrated that bona fide iPSCs are, if not identical, very similar to ES cells. Likewise, cloned mice have been obtained from mouse iPSCs by the NT method3. These studies indicate that iPSCs can substitute ES cells for the purpose of genomic manipulation.

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