REDUCTION IN THE NUMBER OF SPINAL MOTOR-NEURONS IN NEUROTROPHIN-3-DEFICIENT MICE

REDUCTION IN THE NUMBER OF SPINAL MOTOR-NEURONS IN NEUROTROPHIN-3-DEFICIENT MICE
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DOI:
10.1016/0306-4522(95)00221-4
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发表时间:
1995-11-01
期刊:
影响因子:
3.3
通讯作者:
JAENISCH, R
JAENISCH, R
中科院分区:
医学3区
文献类型:
--
作者:
KUCERA, J;ERNFORS, P;JAENISCH, R

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通过测定神经营养素-3基因缺失的小鼠腰腹侧脊神经根中有髓神经纤维的数量来评估神经营养素-3缺乏对脊髓运动神经元的影响。很少或没有小口径(fusimotor)神经纤维存在于L4腹根的纯合突变小鼠缺乏两个拷贝的神经营养因子-3基因,和大约一半的正常补体的纤维存在于杂合小鼠有一个拷贝的神经营养因子-3基因相对于野生型小鼠在两周龄。在后肢肌肉中,梭运动神经纤维的数量与梭运动神经支配的靶器官肌梭的数量成正比。肌梭和梭内纤维在纯合突变体的比目鱼肌中不存在,并且与先前的报道雅阁,在杂合相对于野生型小鼠中减少了约50%。神经营养素-3可能由梭内纤维产生,并可能为发育中的梭运动神经元提供靶源性神经营养支持,因为在没有肌梭的情况下,神经元不分化和/或存活。与此相反,大多数支配梭外肌纤维的骨骼运动神经元在缺乏神经营养素-3的情况下正常分化。本研究结合我们以前报道的数据进行分析,表明神经营养素-3以协调的方式直接或间接地支持三类细胞中的每一类细胞的发育-Ia和Ib感觉神经元,梭运动神经元,和肌梭内肌纤维--它们构成肢体本体感受系统。
The effects of a deficiency of neurotrophin-3 on spinal motor neurons were assessed by determining the number of myelinated nerve fibers in lumbar ventral spinal roots of mice with a deletion in the neurotrophin-3 gene. Few or no small-caliber (fusimotor) nerve fibers were present in the L4 ventral root of homozygous mutant mice lacking both copies of the neurotrophin-3 gene, and approximately one-half of the normal complement of the fibers was present in heterozygous mice having one copy of the neurotrophin-3 gene relative to wild type mice at two weeks of age. Numbers of fusimotor nerve fibers paralleled numbers of muscle spindles, the target organs of fusimotor innervation, in hindlimb muscles. Muscle spindles and intrafusal fibers were absent in the soleus muscles of homozygous mutants, and were reduced by approximately 50% in heterozygous relative to wild type mice in accord with previous reports. Neurotrophin-3 might be generated by the intrafusal fibers and may provide a target-derived neurotrophic support for developing fusimotor neurons because in the absence of muscle spindles the neurons did not differentiate and/or survive. In contrast, a great majority of skeletomotor neurons that innervate extrafusal muscle fibers differentiated normally in the absence of neurotrophin-3.This study, analysed in conjunction with our previously reported data, suggests that neurotrophin-3 acts in a coordinated fashion to support, either directly or indirectly, the development of each of the three classes of cells-Ia and Ib sensory neurons, fusimotor neurons, and intrafusal muscle fibers-that comprise the limb proprioceptive system.