A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator
A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator
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DOI：
10.1038/ng0797-226
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发表时间：
1997-07-01
期刊：
影响因子：
30.8
通讯作者：
Wallace, DC
中科院分区：
文献类型：
--
作者：
Graham, BH;Waymire, KG;Wallace, DC
为了创建组织特异性线粒体疾病的动物模型，我们产生了缺乏腺嘌呤核苷酸转位子（Ant1）的心脏/肌肉异构体的“敲除”小鼠。抗无效突变体骨骼肌的组织学和超微结构检查显示肌肉纤维呈红色，线粒体增生，心脏检查显示心肌肥大，线粒体增生。从突变骨骼肌中分离的线粒体在耦合呼吸中表现出严重的缺陷。Ant1突变成人的静息血清乳酸水平也比对照组高4倍，表明代谢性酸中毒。值得注意的是，突变成人表现出严重的运动不耐受。因此，抗突变小鼠具有线粒体肌病和心肌病的生化、组织学、代谢和生理特征。
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 Anti 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, Anti mutant mice have the biochemical, histological, metabolic and physiological characteristics of mitochondrial myopathy and cardiomyopathy.