GIBH scientists have successfully produced the world’s first Rosa26-targeted swine model

Recently, Prof Liangxue Lai from GIBH and Animal Hospital of Jilin University in collaboration with Prof Zhong Wang from the University of Michigan have for the first time identified and characterized the porcine Rosa26 locus and successfully produced the world’s first Rosa26-targeted swine model through recombinase-mediated cassette exchange (RMCE). The pRosa26-targeted pigs, together with the RMCE strategy reported by Prof Lai and Prof Wang will serve as an excellent platform for generating genetically modified pigs for biomedical and agricultural applications. This work has been published online in Cell Research on the 7th of Feb 2014.

Genetic modification of pigs has many agricultural and biomedical applications. Ectopic overexpression of foreign genes is necessary in many cases to generate transgenic pigs with favorable phenotypes. However, random integration of foreign genes often leads to unpredictable expression and unstable phenotypes. By taking advantage of recently emerging technology of gene editing mediated by transcription activator-like effector nuclease (TALEN), the research groups led by Prof Lai and Prof Wang have characterized the porcine Rosa-26 (pRosa26) locus and targeted a Cre-dependent reporter gene into the pRosa26 locus. Using this approach, they are able to create transgenic pigs stably overexpressing a gene of interest through RMCE.

In addition, the research groups led by Prof Lai and Prof Wang have also successfully introduced a heterologous loxP sites into Rosa26 locus using RMCE so that EGFP gene can be replaced by a red fluorescent protein tdTomato gene. In this way, they generated the world’s first RMCE large animal model. Using this model, the scientists can use RMCE to exchange any gene by inserting the gene into the Rosa26 locus so that the target gene shows no differences in expression level in all tissues of large animals. Since RMCE mediated gene exchange can be obtained without drug selection, therefore the transgenic pigs generated do not carry any exogenous drug resistance gene. Thus, transgenic pigs generated in this way can greatly reduce biosecurity and food safety risks.

The research carried out by Prof Lai and Prof Wang’s groups are funded by the National Science and Technology Department "Significant foundation Research Program" and the U.S. National Institutes of Health (NIH).