Motor neuron rescue in spinal muscular atrophy mice demonstrates that sensory-motor defects are a consequence, not a cause, of motor neuron dysfunction.
Motor neuron rescue in spinal muscular atrophy mice demonstrates that sensory-motor defects are a consequence, not a cause, of motor neuron dysfunction.
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DOI：
10.1523/jneurosci.5775-11.2012
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发表时间：
2012-03-14
期刊：
影响因子：
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通讯作者：
Didonato CJ
中科院分区：
文献类型：
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作者：
Gogliotti RG;Quinlan KA;Barlow CB;Heier CR;Heckman CJ;Didonato CJ
运动神经元（MN）的丧失是神经肌肉疾病脊髓性肌萎缩症（SMA）的一个标志；然而，尚不清楚这种表型是否自主起源于 MN 内。为了解决这个问题，我们开发了一种严重 SMA 的诱导小鼠模型，该模型的存活率和运动功能、运动单位病理学和过度兴奋的 MN 均降低。使用 Hb9-Cre 等位基因，我们自主增加了 MN 内的 Smn 水平，并证明 MN 救援显着改善了 SMA 小鼠中常见的所有表型和病理。 MN 救援还可以纠正 SMA 运动神经元的过度兴奋，并防止感觉运动突触剥离。 MN 拯救的 SMA 小鼠的存活期仅延长 5 天，部分原因是心脏自主神经支配失败。总的来说，这项工作表明 SMA 表型自主起源于 MN，并且感觉运动突触丧失是 MN 功能障碍的结果，而不是原因。
The loss of motor neurons (MN) is a hallmark of the neuromuscular disease spinal muscular atrophy (SMA); however it is unclear whether this phenotype autonomously originates within the MN. To address this question, we developed an inducible mouse model of severe SMA that has reduced survival and motor function, motor unit pathology and hyperexcitable MNs. Using an Hb9-Cre allele, we increased Smn levels autonomously within MNs, and demonstrate that MN-rescue significantly improves all phenotypes and pathologies commonly described in SMA mice. MN-rescue also corrects the hyperexcitability in SMA motor neurons, and prevents sensory-motor synaptic stripping. Survival in MN-rescued SMA mice is extended by only 5 days, due in part to failed autonomic innervation of the heart. Collectively, this work demonstrates that the SMA phenotype autonomously originates in MNs and that sensory-motor synapse loss is a consequence, not a cause, of MN dysfunction.