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Neuromuscul Disord. 2004 May;14(5):329-36.

Identification of the RAG-1 as a suitable mouse model for mitochondrial DNA disease.

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Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.


Previous studies have shown that transfer of human myoblasts carrying a mitochondrial DNA mutation into muscles of the severe combined immunodeficient mouse may provide an important animal model for mitochondrial myopathy. However, a major drawback of this mouse is its extreme sensitivity to ionising radiation, a pre-treatment which enhances the efficiency of myoblast transfer success. We implanted human myoblasts into the tibialis anterior muscles of another immunodeficient mouse, mutated in the recombinase activating gene-1 (RAG-1), to determine if this mouse could be an alternative to the severe combined immunodeficient for our mitochondrial myoblast transfer model. We also examined several different methods of muscle degeneration prior to myoblast transfer to determine which method resulted in the greatest amount of human tissue in implanted muscles. Our results show that the RAG-1 mouse displayed no sensitivity to the irradiation process compared to the high sensitivity in the severe combined immunodeficient mouse which resulted in early termination of the study. We also show that degeneration of host muscles by the myotoxin barium chloride (BaCl(2)) resulted in the greatest amount of regenerating human muscle fibres in both the severe combined immunodeficient and RAG-1 mice. In addition, the maximum amount of human fibres observed in transplanted muscles was similar in each mouse strain. The average number of fibres throughout muscles was significantly greater in severe combined immunodeficient mice injured by BaCl(2), but was similar between all other muscle groups. This study suggests that the RAG-1 mouse is a suitable host for the mitochondrial myoblast transfer model and may also prove valuable for other myoblast transfer models such as muscular dystrophy.

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