Neurotrophin-3 ameliorates sensory-motor deficits in Er81-deficient mice.
Neurotrophin-3 ameliorates sensory-motor deficits in Er81-deficient mice.
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Neurotropin-3 可改善 Er81 缺陷小鼠的感觉运动缺陷。
DOI：
10.1002/dvdy.20964
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
Kucera,J
中科院分区：
文献类型：
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作者：
Li,LY;Wang,Z;Sedý,J;Quazi,R;Walro,JM;Frank,E;Kucera,J
ETS转录因子ER 81和骨骼肌源性神经营养因子3（NT 3）是脊髓中肌梭形成和梭传入运动神经元突触功能所必需的两种因子。在Er 81基因敲除小鼠中，脊髓完全退化或异常，并且纺锤体传入不能投射到脊髓运动神经元;然而，在传入神经元和肌梭发育过程中，ER 81和NT 3之间的相互作用知之甚少。为了检查在缺乏ER 81的情况下，肌肉中NT 3的过表达是否能拯救纺锤体和传入运动神经元的连接，我们产生了myoNT 3; ER 81 −/−双突变小鼠，这些小鼠在缺乏ER 81的情况下选择性地在肌肉中过表达NT 3。MyoNT 3; Er 81 −/−突变体的纺锤体反射弧与Er 81缺失小鼠有很大差异。在myoNT 3; Er 81 −/−小鼠中，肌梭密度更大，投射到腹侧脊髓的传入神经更多。myoNT 3的特异性; Er 81 −/−肌肉对重复的肌肉轻敲反应正常，从Ia传入神经到运动神经元的单突触输入在Er 81 −/−突变体中显著减少，在myoNT 3; Er 81 −/−小鼠中恢复到野生型水平。因此，过量的肌源性NT 3逆转了由缺乏ER 81诱导的纺锤体数量和传入功能的缺陷。我们的结论是，肌源性NT 3可以独立于ER 81调节纺锤体密度和传入运动神经元连接。发展动力学235：3039-3050，2006年。© 2006 Wiley利斯公司
Two factors, the ETS transcription factor ER81 and skeletal muscle‐derived neurotrophin‐3 (NT3), are essential for the formation of muscle spindles and the function of spindle afferent–motoneuron synapses in the spinal cord. Spindles either degenerate completely or are abnormal, and spindle afferents fail to project to spinal motoneurons inEr81null mice; however, the interactions between ER81 and NT3 during the processes of afferent neuron and muscle spindle development are poorly understood. To examine if overexpression of NT3 in muscle rescues spindles and afferent–motoneuron connectivity in the absence of ER81, we generatedmyoNT3;Er81−/−double‐mutant mice that selectively overexpress NT3 in muscle in the absence of ER81. Spindle reflex arcs inmyoNT3;Er81−/−mutants differed greatly fromEr81null mice. Muscle spindle densities were greater and more afferents projected into the ventral spinal cord inmyoNT3;Er81−/−mice. Spindles ofmyoNT3;Er81−/−muscles responded normally to repetitive muscle taps, and the monosynaptic inputs from Ia afferents to motoneurons, grossly reduced inEr81−/−mutants, were restored to wild‐type levels inmyoNT3;Er81−/−mice. Thus, an excess of muscle‐derived NT3 reverses deficits in spindle numbers and afferent function induced by the absence of ER81. We conclude that muscle‐derived NT3 can modulate spindle density and afferent–motoneuron connectivity independently of ER81. Developmental Dynamics 235:3039–3050, 2006. © 2006 Wiley‐Liss, Inc.