A mutation in alpha-tropomyosin(slow) affects muscle strength, maturation and hypertrophy in a mouse model for nemaline myopathy.
A mutation in alpha-tropomyosin(slow) affects muscle strength, maturation and hypertrophy in a mouse model for nemaline myopathy.
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α-原肌球蛋白（慢）突变会影响线状肌病小鼠模型的肌肉力量、成熟和肥大。
DOI：
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发表时间：
2001
影响因子：
3.5
通讯作者：
E. Hardeman
中科院分区：
文献类型：
--
作者：
M. Corbett;Stephen Robinson;G. Dunglison;N. Yang;J. Joya;Angus W. Stewart.;C. Schnell;P. Gunning;K. North;E. Hardeman
线状肌病是一种遗传性骨骼肌疾病，其定义是肌节单位内电子致密堆积的独特病理，称为杆状，肌肉无力，在大多数情况下，以缓慢的氧化(1型)纤维为主。我们建立了一个转基因小鼠模型来研究这种疾病，方法是表达先前在人类队列中发现的α-原肌球蛋白的常染色体显性突变(慢)。在所有肌肉中都发现了杆状蛋白，但程度不同，与存在的突变蛋白的数量无关。此外，在小鼠中发现了一种通常与这种疾病无关的病理特征--细胞质小体，随后在人类样本中进行了鉴定。肌肉无力是这种疾病的一个主要特征，并从纤维成分、含有杆状纤维的程度、纤维力学和纤维直径方面进行了检查。2个月龄时快速糖酵解(2B型)纤维明显肥大。在5-6个月大的小鼠中，肌肉无力明显，这与这种突变在人类中观察到的晚发型相似。较晚的发病与观察到的纤维类型和视杆病理改变无关。相反，肌肉无力的出现与与年龄相关的纤维直径的减少有关，并表明快速糖酵解纤维的肥大可以防止早期发病。我们认为，临床表型是由于肥大未能持续，从而弥补了肌肉无力所致。
Nemaline myopathy is a hereditary disease of skeletal muscle defined by a distinct pathology of electron-dense accumulations within the sarcomeric units called rods, muscle weakness and, in most cases, a slow oxidative (type 1) fiber predominance. We generated a transgenic mouse model to study this disorder by expressing an autosomal dominant mutant of alpha-tropomyosin(slow) previously identified in a human cohort. Rods were found in all muscles, but to varying extents which did not correlate with the amount of mutant protein present. In addition, a pathological feature not commonly associated with this disorder, cytoplasmic bodies, was found in the mouse and subsequently identified in human samples. Muscle weakness is a major feature of this disease and was examined with respect to fiber composition, degree of rod-containing fibers, fiber mechanics and fiber diameter. Hypertrophy of fast, glycolytic (type 2B) fibers was apparent at 2 months of age. Muscle weakness was apparent in mice at 5-6 months of age, mimicking the late onset observed in humans with this mutation. The late onset did not correlate with observed changes in fiber type and rod pathology. Rather, the onset of muscle weakness correlates with an age-related decrease in fiber diameter and suggests that early onset is prevented by hypertrophy of fast, glycolytic fibers. We suggest that the clinical phenotype is precipitated by a failure of the hypertrophy to persist and therefore compensate for muscle weakness.
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影响因子：
--
作者：
G. Pfeifer;A. Riggs
通讯作者：
G. Pfeifer;A. Riggs
DOI：
10.1073/pnas.96.5.2305
发表时间：
1999-03-02
影响因子：
11.1
作者：
Pelin, K;Hilpelä, P;Wallgren-Pettersson, C
通讯作者：
Wallgren-Pettersson, C
营养不良小鼠膈肌肌球蛋白重链表达和收缩功能的适应。
DOI：
10.1152/ajpcell.1993.265.3.c834
发表时间：
1993
期刊：
The American journal of physiology
影响因子：
--
作者：
Petrof,BJ;Stedman,HH;Shrager,JB;Eby,J;Sweeney,HL;Kelly,AM
通讯作者：
Kelly,AM
肌动蛋白结合位点和血影蛋白重复序列将肌节α-肌动蛋白靶向体内成熟Z带的可分配性：对体外结合研究的影响。
DOI：
10.1006/dbio.1998.8920
发表时间：
1998
期刊：
Developmental biology.
影响因子：
--
作者：
Lin,Z;Hijikata,T;Zhang,Z;Choi,J;Holtzer,S;Sweeney,HL;Holtzer,H
通讯作者：
Holtzer,H