A new immunodeficient mouse model for human myoblast transplantation

Design of efficient transplantation strategies for myoblast-based gene ther apies in humans requires animal models in which xenografts are tolerated fo r long periods of time. In addition, such recipients should be able to with stand pretransplantation manipulations for enhancement of graft growth. Her e we report that a newly developed immunodeficient mouse carrying two known mutations (the recombinase activating gene 2, RAG2, and the common cytokin e receptor gamma, gammac) is a candidate fulfilling these requirements. Ske letal muscles from RAG2(-/-)/gammac(-/-) double mutant mice recover normall y after myotoxin application or cryolesion, procedures commonly used to ind uce regeneration and improve transplantation efficiency. Well-differentiate d donor-derived muscle tissue could be detected up to 9 weeks after transpl antation of human myoblasts into RAG2(-/-)/gammac(-/-) muscles. These resul ts suggest that the RAG2(-/-)/gammac(-/-) mouse model will provide new oppo rtunities for human muscle research.