Failure of lower motor neuron radial outgrowth precedes retrograde degeneration in a feline model of spinal muscular atrophy.
Failure of lower motor neuron radial outgrowth precedes retrograde degeneration in a feline model of spinal muscular atrophy.
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在脊髓性肌萎缩的猫模型中，下运动神经元径向生长的失败先于逆行性变性。
DOI：
10.1002/cne.23010
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Fyfe,JohnC
中科院分区：
文献类型：
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作者：
Wakeling,ErinN;Joussemet,Béatrice;Costiou,Patrick;Fanuel,Dominique;Moullier,Philippe;Barkats,Martine;Fyfe,JohnC
猫脊髓性肌萎缩症（SMA）是家猫的一种完全渗透性、常染色体隐性下运动神经元疾病，临床上类似于人SMA III型。全基因组连锁扫描发现了一个140 kb的缺失，消除了LIX 1的表达，LIX 1是一种功能未知的新型SMA候选基因。为了表征猫SMA的进展，我们评估了从3日龄至临床体征发作后的肌肉和脊髓病理变化。肌电图（EMG）分析表明去神经发生在10至12周之间，第一个神经系统体征发生在同一时间。在8-11周时，比目鱼肌和桡侧腕伸肌的复合运动动作电位（CMAP）幅度显著降低。受影响猫的股四头肌肌纤维在10周时看起来较小;到12周时，萎缩纤维比年龄匹配的对照组更普遍。在受影响的猫中，在12周时观察到L5腹根轴突明显缺失。到21周龄时，受影响的猫的L5运动轴突比正常猫少40%。即使在21周时，L5索马细胞总数也没有显著差异;因此，变性开始于细胞体远端，并逆行进行。L5腹根和角的形态测定分析显示，4周前的轴突损失，运动轴突在受影响的猫未能进行径向扩大，这表明一个假定的疾病基因LIX 1在轴突的径向生长的作用。神经学比较杂志520：1737-1750，2012。© 2011 Wiley Periodicals，Inc.
Feline spinal muscular atrophy (SMA) is a fully penetrant, autosomal recessive lower motor neuron disease in domestic cats that clinically resembles human SMA Type III. A whole genome linkage scan identified a ∼140‐kb deletion that abrogates expression ofLIX1, a novel SMA candidate gene of unknown function. To characterize the progression of feline SMA, we assessed pathological changes in muscle and spinal cord from 3 days of age to beyond onset of clinical signs. Electromyographic (EMG) analysis indicating denervation occurred between 10 and 12 weeks, with the first neurological signs occurring at the same time. Compound motor action potential (CMAP) amplitudes were significantly reduced in the soleus and extensor carpi radialis muscles at 8–11 weeks. Quadriceps femoris muscle fibers from affected cats appeared smaller at 10 weeks; by 12 weeks atrophic fibers were more prevalent than in age‐matched controls. In affected cats, significant loss of L5 ventral root axons was observed at 12 weeks. By 21 weeks of age, affected cats had 40% fewer L5 motor axons than normal. There was no significant difference in total L5 soma number, even at 21 weeks; thus degeneration begins distal to the cell body and proceeds retrogradely. Morphometric analysis of L5 ventral roots and horns revealed that 4 weeks prior to axon loss, motor axons in affected cats failed to undergo radial enlargement, suggesting a role for the putative disease geneLIX1in radial growth of axons. J. Comp. Neurol. 520:1737–1750, 2012. © 2011 Wiley Periodicals, Inc.