Limb proprioceptive deficits without neuronal loss in transgenic mice overexpressing neurotrophin-3 in the developing nervous system.
Limb proprioceptive deficits without neuronal loss in transgenic mice overexpressing neurotrophin-3 in the developing nervous system.
复制标题
在发育中的神经系统中过度表达神经营养素 3 的转基因小鼠中，肢体本体感觉缺陷但没有神经元损失。
作者：
T. Ringstedt;J. Kučera;U. Lendahl;P. Ernfors;C. Ibáñez
在神经营养因子-3(NT3)基因启动子和增强子区域的控制下，在过量表达NT3的转基因小鼠中研究了NT3在感觉神经元发育中的作用。这些小鼠大多在出生后第一天死亡，并且都表现出严重的肢体共济失调，提示肢体本体感觉功能障碍。追踪和组织学分析显示，肢体肌肉中的纺锤体完全丧失，周围和中央Ia投射缺失，背根神经节(DRG)内缺乏对小白蛋白免疫反应的细胞。尽管有这些缺陷，这些小鼠的DRG中没有神经元丢失。出生时，转基因DRG的神经元数量增加，P物质、降钙素基因相关肽和NT3受体trkC表达的神经元比例正常。转基因小鼠的背根在出生时轴突数量增加，这表明转基因小鼠的所有感觉神经元都投射到背髓。尽管没有到达运动神经元的中枢Ia传入，但在转基因脊髓的中线，可以看到几个感觉纤维向异位高水平的NT3投射。这些发现表明，NT3在本体感觉神经元的分化、靶向侵袭和Ia投射的形成中发挥了新的作用，这些作用不依赖于它对神经元存活的影响。
The role of neurotrophin-3 (NT3) during sensory neuron development was investigated in transgenic mice overexpressing NT3 under the control of the promoter and enhancer regions of the nestin gene, an intermediate filament gene widely expressed in the developing nervous system. Most of these mice died during the first postnatal day, and all showed severe limb ataxia suggestive of limb proprioceptive dysfunction. Tracing and histological analyses revealed a complete loss of spindles in limb muscles, absence of peripheral and central Ia projections, and lack of cells immunoreactive to parvalbumin in the dorsal root ganglion (DRG). Despite these deficits, there was no neuronal loss in the DRG of these mice. At birth, transgenic DRG showed increased neuron numbers, and displayed a normal proportion of neurons expressing substance P, calcitonin gene-related peptide and the NT3 receptor trkC. Transgenic dorsal roots exhibited an increased number of axons at birth, indicating that all sensory neurons in transgenic mice projected to the dorsal spinal cord. Despite the absence of central Ia afferents reaching motorneurons, several sensory fibers were seen projecting towards ectopic high levels of NT3 in the midline of transgenic spinal cords. These findings suggest novel roles for NT3 in differentiation of proprioceptive neurons, target invasion and formation of Ia projections which are independent from its effects on neuronal survival.
在正常细胞死亡期间，肌肉感觉神经元需要来自外周组织的神经营养蛋白-3。
DOI：
10.1242/dev.121.5.1341
发表时间：
1995
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Oakley,RA;Garner,AS;Large,TH;Frank,E
通讯作者：
Frank,E
DOI：
10.1073/pnas.91.25.11844
发表时间：
1994-12-06
影响因子：
11.1
作者：
TESSAROLLO, L;VOGEL, KS;PARADA, LF
通讯作者：
PARADA, LF