A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator

Nat Genet. 1997 Jul;16(3):226-34. doi: 10.1038/ng0797-226.


In an attempt to create an animal model of tissue-specific mitochondrial disease, we generated 'knockout' mice deficient in the heart/muscle isoform of the adenine nucleotide translocator (Ant1). Histological and ultrastructural examination of skeletal muscle from Ant1 null mutants revealed ragged-red muscle fibers and a dramatic proliferation of mitochondria, while examination of the heart revealed cardiac hypertrophy with mitochondrial proliferation. Mitochondria isolated from mutant skeletal muscle exhibited a severe defect in coupled respiration. Ant1 mutant adults also had a resting serum lactate level fourfold higher than that of controls, indicative of metabolic acidosis. Significantly, mutant adults manifested severe exercise intolerance. Therefore, Ant1 mutant mice have the biochemical, histological, metabolic and physiological characteristics of mitochondrial myopathy and cardiomyopathy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cardiomegaly / genetics
  • Cardiomegaly / pathology
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / pathology
  • Cell Respiration
  • Cloning, Molecular
  • Disease Models, Animal*
  • Mice
  • Mice, Knockout
  • Mitochondria, Muscle / genetics
  • Mitochondria, Muscle / metabolism*
  • Mitochondria, Muscle / ultrastructure
  • Mitochondrial ADP, ATP Translocases / deficiency
  • Mitochondrial ADP, ATP Translocases / genetics*
  • Mitochondrial ADP, ATP Translocases / metabolism
  • Mitochondrial Myopathies / genetics*
  • Mitochondrial Myopathies / metabolism
  • Mitochondrial Myopathies / pathology
  • Molecular Sequence Data
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Oxidative Phosphorylation
  • Physical Exertion
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Stem Cells / pathology


  • RNA, Messenger
  • Mitochondrial ADP, ATP Translocases