Journal article

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

BH Graham, KG Waymire, B Cottrell, IA Trounce, GR MacGregor, DC Wallace

Nature Genetics | NATURE PUBLISHING CO | Published : 1997

Abstract

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. Significantl..

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University of Melbourne Researchers