Researchers Evaluate Health of Transgenic Donor Pigs Expressing Five Human Genes

Genetic manipulation of pigs designated for xenotransplantation has shown considerable promise on xenograft survival in primates. However, modification of genes in donor pigs via knock-out/knock-in technologies to enhance tolerance against transplanted organs in the recipients has not been evaluated for health issues in donor pigs.

The team of Dae-Jin Kwon from National Institute of Animal Science in South Korea developed transgenic Massachusetts General Hospital piglets by knocking-out the α-1,3-galactosyltransferase (GT) gene and by simultaneously knocking-in five different human genes, including, DAF, CD39, TFPI, C1 inhibitor (C1-INH), and TNFAIP3 (A20).

All five individual protein products were successfully produced in the newborn transgenic pigs. While primary tests revealed no abnormality in transgenic piglets, further examination found that the transgenic piglets had abnormally low numbers of platelets, white blood cells, and lymphocytes. However, the transgenic piglets had similar numbers of red blood cells compared to the control littermate piglets.

The study suggests that transgenic expression of up to five different genes can be achieved. The study also provides basis for determining optimum dosages of transgene expression to produce transgenic donor pigs without health issues.

For more on this study, read the full article in Transgenic Research.