Force impairment in calpain 3-deficient mice is not correlated with mechanical disruption
Force impairment in calpain 3-deficient mice is not correlated with mechanical disruption
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DOI：
10.1002/mus.10368
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发表时间：
2003-05-01
期刊：
影响因子：
3.4
通讯作者：
Raymackers, JM
中科院分区：
文献类型：
--
作者：
Fougerousse, F;Gonin, P;Raymackers, JM
人类钙蛋白酶3的缺陷是导致肢带型肌营养不良症2A型的原因，这是一种常染色体隐性遗传疾病，其主要特征是迟发性近端肌萎缩。先前已经通过基因靶向产生了相应的鼠模型。在这份报告中，钙蛋白酶3缺陷（capn 3（-/-））小鼠的肌肉活动在不同年龄进行了评估。生长曲线显示进行性全身肌肉萎缩。在小鼠的整个生命周期中进行的组织学检查证实了营养不良性病变。整个动物试验表明，只有轻微的重大损害的前肢。对选定的分离的快肌和慢肌的机械特性的研究表明，capn 3（-/-）小鼠的慢肌明显弱于野生型小鼠。三种不同的测试表明，没有膜破坏，这表明capn 3（-/-）小鼠营养不良的非机械病因。这些发现与涉及信号系统的机制一致。
Defects in human calpain 3 are responsible for limb-girdle muscular dystrophy type 2A, an autosomal-recessive disorder characterized mainly by late-onset proximal muscular atrophy. A corresponding murine model has previously been generated by gene targeting. In this report, muscular activity of calpain 3-deficient (capn3(-/-)) mice was evaluated at different ages. Growth curves showed a progressive global muscular atrophy. Histological examination throughout the lifespan of mice confirmed the dystrophic lesions. Whole animal tests showed only a mild significant impairment of the forelimbs. Studies of the mechanical properties of selected isolated fast- and slow-twitch muscles demonstrated that slow-twitch muscles were significantly weaker in capn3(-/-) mice than in wild-type mice. Three different tests showed that there was no membrane disruption, suggesting a nonmechanical etiology of capn3(-/-) mice dystrophy. These findings are consistent with a mechanism involving signaling systems.