A new immunodeficient mouse model for human myoblast transplantation

Hum Gene Ther. 2001 May 1;12(7):823-31. doi: 10.1089/104303401750148784.


Design of efficient transplantation strategies for myoblast-based gene therapies in humans requires animal models in which xenografts are tolerated for long periods of time. In addition, such recipients should be able to withstand pretransplantation manipulations for enhancement of graft growth. Here we report that a newly developed immunodeficient mouse carrying two known mutations (the recombinase activating gene 2, RAG2, and the common cytokine receptor gamma, gammac) is a candidate fulfilling these requirements. Skeletal muscles from RAG2(-/-)/gammac(-/-) double mutant mice recover normally after myotoxin application or cryolesion, procedures commonly used to induce regeneration and improve transplantation efficiency. Well-differentiated donor-derived muscle tissue could be detected up to 9 weeks after transplantation of human myoblasts into RAG2(-/-)/gammac(-/-) muscles. These results suggest that the RAG2(-/-)/gammac(-/-) mouse model will provide new opportunities for human muscle research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Division / drug effects
  • Cell Transplantation*
  • Cobra Cardiotoxin Proteins / pharmacology
  • DNA-Binding Proteins / genetics
  • Dystrophin / analysis
  • Gene Deletion
  • Genetic Therapy / methods*
  • Humans
  • Immunohistochemistry
  • Interleukin Receptor Common gamma Subunit
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Microscopy, Fluorescence
  • Models, Animal*
  • Muscle, Skeletal / cytology*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / immunology*
  • Muscle, Skeletal / metabolism
  • Nuclear Proteins
  • Receptors, Interleukin-7 / genetics
  • Regeneration / drug effects
  • Transplantation Tolerance* / drug effects
  • Transplantation Tolerance* / genetics
  • Transplantation Tolerance* / immunology
  • Transplantation, Heterologous


  • Cobra Cardiotoxin Proteins
  • DNA-Binding Proteins
  • Dystrophin
  • IL2RG protein, human
  • Il2rg protein, mouse
  • Interleukin Receptor Common gamma Subunit
  • Nuclear Proteins
  • RAG2 protein, human
  • Rag2 protein, mouse
  • Receptors, Interleukin-7
  • V(D)J recombination activating protein 2