Growth and muscle defects in mice lacking adult myosin heavy chain genes.
Growth and muscle defects in mice lacking adult myosin heavy chain genes.
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DOI：
10.1083/jcb.139.5.1219
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发表时间：
1997-12-01
期刊：
影响因子：
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通讯作者：
Kucherlapati R
中科院分区：
文献类型：
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作者：
Acakpo-Satchivi LJ;Edelmann W;Sartorius C;Lu BD;Wahr PA;Watkins SC;Metzger JM;Leinwand L;Kucherlapati R
三个成人快肌球蛋白重链 (MyHC) 构成成人骨骼肌系统中肌球蛋白的绝大多数，并且相同性 >92%。我们描述了在两个主要的成体快速 MyHC 基因 IIb 和 IId/x 中携带无效突变的小鼠。两种无效品系均表现出生长和肌肉缺陷，但两种品系之间的缺陷不同，并且与每种基因产物的丰度或分布不相关。例如，尽管事实上 MyHC-IIb 占骨骼肌中肌球蛋白的 70% 以上，并且表现出最广泛的表达分布，但 IIb 无效突变体的表型通常比 MyHC-IId/x 无效菌株更温和。此外，在野生型小鼠中同时表达IIb和IId/x MyHC的肌肉中，两种基因无效表达的组织学缺陷完全不同。最引人注目的是，虽然两种零应变都在孤立的肌肉中表现出生理缺陷，但这些缺陷是明显的。 IIb 缺失小鼠的肌肉产生力的能力显着降低，而 IId 缺失小鼠的肌肉产生正常量的力，但动力学特性发生了改变。这些小鼠表现出的许多表型是人类肌肉疾病的典型表型，应该有助于深入了解其病因学。
The three adult fast myosin heavy chains (MyHCs) constitute the vast majority of the myosin in adult skeletal musculature, and are >92% identical. We describe mice carrying null mutations in each of two predominant adult fast MyHC genes, IIb and IId/x. Both null strains exhibit growth and muscle defects, but the defects are different between the two strains and do not correlate with the abundance or distribution of each gene product. For example, despite the fact that MyHC-IIb accounts for >70% of the myosin in skeletal muscle and shows the broadest distribution of expression, the phenotypes of IIb null mutants are generally milder than in the MyHC-IId/x null strain. In addition, in a muscle which expresses both IIb and IId/x MyHC in wild-type mice, the histological defects are completely different for null expression of the two genes. Most striking is that while both null strains exhibit physiological defects in isolated muscles, the defects are distinct. Muscle from IIb null mice has significantly reduced ability to generate force while IId null mouse muscle generates normal amounts of force, but has altered kinetic properties. Many of the phenotypes demonstrated by these mice are typical in human muscle disease and should provide insight into their etiology.