Development of RAG2 ^-/- IL2Rγ ^-/Y immune deficient FAH-knockout miniature pig.

ABSTRACT: Human hepatocyte transplantation for liver disease treatment have been hampered by the lack of quality human hepatocytes. Pigs with their large body size, longevity and physiological similarities with human are appropriate animal models for the in vivo expansion of human hepatocytes. Here we report on the generation of RAG2^-/-IL2Rγ^-/YFAH^-/- (RGFKO) pigs via CRISPR/Cas9 system and somatic cell nuclear transfer. We showed that thymic and splenic development in RGFKO pigs was impaired. V(D)J recombination processes were also inactivated. Consequently, RGFKO pigs had significantly reduced numbers of porcine T, B and NK cells. Moreover, due to the loss of FAH, porcine hepatocytes continuously undergo apoptosis and consequently suffer hepatic damage

SUBMITTER: Zhao H 

PROVIDER: S-EPMC9400017 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature