The Scientists in GIBH Created Immune-deficient Rabbits by Using TALEN Technology

Recently, a research group led by Prof. Liangxue Lai and Duanqing Pei has successfully applied transcription activator-like effector nucleases (TALENs) to rabbit gene targeting and established a high-efficiency technique platform for specific genetic modification in rabbit. Based on this platform, immune-deficient rabbits were generated for the first time in the world by disrupting RAG genes, which is responsible for V(D)J recombination in primary lymphoid to generate mature B and T cells. This work had been published online by Cell Research. 

Rabbit is an important experimental animal. Gene modification in rabbits will promote their application in biomedicine research. However, specific genetic modification in rabbit is difficult because no germline-competent ES cells are available and the efficiency of rabbit cloning is extremely low. So far, only one gene targeting rabbit has been reported. Recently, TALEN, a new emerging genome-modifying technology has been employed for in vivo genetic engineering in some animals. Prof. Liangxue Lai and Duanqing Pei’s team made efforts for the first time to use TALENs to disrupt gene in rabbit. The targeting efficiency was more than 90% and biallelically modified efficiency was as high as 60%. The achievements pave the way for specific genetic modification in rabbits in large scale.  

The deficiency of RAG gene blocks maturation of T cells and B cells, and subsequently results in the loss of most immune functions in these rabbits. RAG-deficient rabbits without mature T and B cells could be used as valuable animal models for drug discovery, xenotransplantation and stem cell therapy for human diseases. 

This work was supported by grants from National Science and Technology Major Project (XDA01020107). 

                                                                 15days after the birth of immune-deficient rabbits