PRNP Gene Disruption In Goat IPSCs Mediated By TALENs

Scrapie, known as the transmissible spongiform encephalopathy (TSE) in goat, is a lethal neurodegenerative disorder that causes great loss on animal husbandry. The transmissible agent (prion) responsible for scrapie is believed to be a modified form of a normal host protein PrPc, which is encoded by the single copy gene PRNP. Depletion of PRNP gene is considered to confer animals resistant to scrapie disease. Although PRNP knockout goat has been generated via somatic cell gene targeting and 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+/- giPSC lines. The PRNP knockout goat iPSCs reported here might be used to generate scrapie-resistant goats efficiently by nuclear transfer or chimeric technology.