Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons.
Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons.
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DOI：
10.1016/j.ydbio.2011.05.667
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发表时间：
2011-08-15
影响因子：
2.7
通讯作者：
Thompson W
中科院分区：
文献类型：
--
作者：
Lee YI;Mikesh M;Smith I;Rimer M;Thompson W
使用毁灭性人类疾病“脊髓性肌萎缩症”（SMA）的小鼠模型来研究这些动物在接近出生后第2周结束时死亡之前的严重肌无力和痉挛。比目鱼肌的运动单位计数以及比目鱼肌神经轴突的计数显示运动神经元没有损失。同样，神经肌肉接头的免疫染色和神经刺激产生的张力测量均未证明神经肌肉传递存在任何显著损伤，即使动物通过补充饮食维持长达5天。然而，肌肉明显较弱，产生的张力不到正常张力的一半。研究中检查的3块肌肉的虚弱似乎是由于肌肉纤维尺寸严重但均匀的减少。尺寸减小的原因是出生后早期发育期间肌纤维生长失败，以及比目鱼肌中产生的纤维数量减少。在这些突变动物中，神经肌肉发育严重延迟：肌球蛋白重链亚型的表达，多神经元神经支配的消除，AChR斑块形状的成熟，SC在连接处的到达及其对神经末梢的覆盖，连接褶皱的发展。因此，如果SMA在这个特定的小鼠是一种运动神经元疾病，它可以以一种不会导致它们死亡或与它们的目标断开连接的方式起作用，但仍然改变了神经肌肉发育的许多方面。
A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precedes the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any significant impairment in neuromuscular transmission, even when animals were maintained up to 5 days longer via a supplementary diet. However, the muscles were clearly weaker, generating less than half their normal tension. Weakness in 3 muscles examined in the study appears due to a severe but uniform reduction in muscle fiber size. The size reduction results from a failure of muscle fibers to grow during early postnatal development and, in soleus, to a reduction in number of fibers generated. Neuromuscular development is severely delayed in these mutant animals: expression of myosin heavy chain isoforms, the elimination of polyneuronal innervation, the maturation in the shape of the AChR plaque, the arrival of SCs at the junctions and their coverage of the nerve terminal, the development of junctional folds. Thus, if SMA in this particular mouse is a disease of motor neurons, it can act in a manner that does not result in their death or disconnection from their targets but nonetheless alters many aspects of neuromuscular development.
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影响因子：
46.9
作者：
通讯作者：
--
影响因子：
2.7
作者：
CONDON, K;SILBERSTEIN, L;THOMPSON, WJ
通讯作者：
THOMPSON, WJ
DOI：
10.1073/pnas.90.5.2040
发表时间：
1993-03-01
影响因子：
11.1
作者：
DUTTON, EK;SIMON, AM;BURDEN, SJ
通讯作者：
BURDEN, SJ
影响因子：
15.9
作者：
Azzouz, M;Le, T;Mazarakis, ND
通讯作者：
Mazarakis, ND
影响因子：
2.4
作者：
BARLOW, B;SANTULLI, TV;SCHULLINGER, JN
通讯作者：
SCHULLINGER, JN