Severe neuropathies in mice with targeted mutations in the ErbB3 receptor
Severe neuropathies in mice with targeted mutations in the ErbB3 receptor
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DOI：
10.1038/39593
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发表时间：
1997-10-16
期刊：
影响因子：
64.8
通讯作者：
Birchmeier, C
中科院分区：
文献类型：
--
作者：
Riethmacher, D;SonnenbergRiethmacher, E;Birchmeier, C
神经调节蛋白及其特异性受体，酪氨酸激酶ErbB家族的成员，参与了雪旺细胞生长和发育的控制（1-3），雪旺细胞是包裹神经轴突以提供电绝缘的特化细胞。在这里，我们使用基因靶向产生缺乏ErbB 3的小鼠，ErbB 3是一种高亲和力的神经调节蛋白受体（4-6）。纯合子erbB 3突变胚胎缺乏许旺细胞前体和许旺细胞，伴随感觉和运动神经元的外周轴突。背根神经节的运动神经元和感觉神经元的初始发育正常发生，但在后期阶段，大多数运动神经元（79%）和背根神经节的感觉神经元（82%）在erbB 3突变胚胎中发生细胞死亡。因此，erbB 3突变幼崽的周围神经系统退化比缺乏神经营养因子或神经营养因子受体的小鼠的细胞死亡严重得多（7，8）。我们还表明，ErbB 3的功能在细胞自主的方式在雪旺细胞的发展，但不是在感觉或运动神经元的生存。我们的研究结果表明，感觉和运动神经元的生存需要的因素，提供了发展中的雪旺细胞。
Neuregulins and their specific receptors, members of the ErbB family of tyrosine kinases, have been implicated in the control of growth and development of Schwann cells(1-3), specialized cells that wrap around nerve axons to provide electrical insulation. Here we use gene targeting to generate mice that lack ErbB3, a high-affinity neuregulin receptor(4-6). Homozygous erbB3 mutant embryos lack Schwann-cell precursors and Schwann cells that accompany peripheral axons of sensory and motor neurons. The initial development of motor neurons and sensory neurons of dorsal root ganglia occurs as it should, but at later stages most motor neurons (79%) and sensory neurons in dorsal root ganglia (82%) undergo cell death in erbB3 mutant embryos. Degeneration of the peripheral nervous system in erbB3 mutant pups is thus much more severe than the cell death in mice that lack neurotrophins or neurotrophin receptors(7,8). We also show that ErbB3 functions in a cell-autonomous way during the development of Schwann cells, but not in the survival of sensory or motor neurons. Our results indicate that sensory and motor neurons require factors for their survival that are provided by developing Schwann cells.