Scrapie, known as the transmissible spongiform encephalopathy (TSE) in goat, is alethal neurodegenerative disorder that causes great loss on animal husbandry.Thetransmissible agent (prion) responsible for scrapie is believed to be a modified formof a normal host protein PrPC, which is encoded by the single copy gene PRNP.Depletion ofPRNP gene is considered to confer animals resistant to scrapie disease.Although PRNP knockout goat has been generated via somatic cell gene targetingand nuclear transfer, the efficiency was extremely low. In this study, we used transcription activator-like effector nuclease (TALEN)technology to generate disruption of a PRNP gene with the efficiencies of 24～50％in goat iPSCs (goat iPSCs), which resulted in establishment of two PRNP+/-giPSClines.The PRNP knockout goat iPSCs reported here might be used to generatescrapie-resistant goats efficiently by nuclear transfer or chimeric technology.