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Publication:

SCID mice containing muscle with human mitochondrial DNA mutations. An animal model for mitochondrial DNA defects (1998)

Author(s): K. M. Clark;D. J. Watt;R. N. Lightowlers;M. A. Johnson;J. B. Relvas;J. W. Taanman;D. M. Turnbull

  • : SCID mice containing muscle with human mitochondrial DNA mutations. An animal model for mitochondrial DNA defects

Abstract: Defects of the mitochondrial genome are important causes of disease. Despite major advances in our investigation of patients, there is no effective therapy. Progress in this area is limited by the absence of any animal models in which we can evaluate treatment. To develop such a model we have injected human myoblasts into the tibialis anterior of SCID mice after inducing necrosis. After injection of normal human myoblasts, regenerating fibers expressed human beta-spectrin, confirming they were derived from fusion of human myoblasts. The stability of the muscle fibers was inferred by demonstrating the formation of motor end plates on the regenerating fibers. In addition, we show the presence of human cytochrome c oxidase subunit II, which is encoded by the mitochondrial genome, in the regenerated fibers. After injection of human myoblasts containing either the A8344G or the T8993C heteroplasmic mitochondrial DNA mutations, human beta-spectrin positive fibers were found to contain the mutation at a similar level to the injected myoblasts. These studies highlight the potential value of this model for the study of mitochondrial DNA defects.

Notes: 0021-9738 Journal Article

  • Short Title: SCID mice containing muscle with human mitochondrial DNA mutations. An animal model for mitochondrial DNA defects
  • Date: Dec 15
  • Journal: J Clin Invest
  • Volume: 102
  • Issue: 12
  • Pages: 2090-5
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Animals Ataxia/genetics Cholinesterases/metabolism DNA, Mitochondrial/*genetics Disease Models, Animal Electron Transport Complex IV/metabolism Gene Expression/genetics Histocytochemistry Humans Mice Mice, SCID Mitochondrial Myopathies/*genetics/pathology Muscle, Skeletal/*immunology/pathology Mutation/*genetics Necrosis Polymorphism, Restriction Fragment Length Regeneration Research Support, Non-U.S. Gov't Retinitis Pigmentosa/genetics Spectrin/metabolism Tissue Transplantation

Staff

Professor Robert Lightowlers
Director, ICaMB and Professor of Molecular Neuroscience