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In zebra fish and rats, direct embryo injection of ZFN-encoding mRNA or plasmids has been employedto generate targeted genome mutations.This method involves unpredictable deletion/insertion mutations in loci, which commonly results in mosaic in first generation offspring.Further tedious breeding isthen necessary to obtain a heritable mutation.In the current study, we have introduced an approachthat combines ZFN and the somatic cell nuclear transfer (SCNT)method to produce gene knock-out (KO) pigs with a defined mutation in peroxisome proliferator-activated receptor gamma (PPAR-γ), as the first gene of interest.