Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons
Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons
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DOI：
10.1016/s0896-6273(00)81087-9
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发表时间：
1999-02-01
期刊：
影响因子：
16.2
通讯作者：
Milbrandt, J
中科院分区：
文献类型：
--
作者：
Heuckeroth, RO;Enomoto, H;Milbrandt, J
Neurturin（NTN）是一种神经元存活因子，在存在GPI连接的辅助受体（GFR α 1或GFR α 2）的情况下激活Ret酪氨酸激酶。通过同源重组产生的neurturin-缺陷（NTN-/-）小鼠是存活的和可生育的，但在肠神经系统中具有缺陷，包括肌间神经丛神经支配密度降低和胃肠运动降低。NTN-/-小鼠中泪腺和下颌下唾液腺的副交感神经支配显著减少，表明Neurturin是副交感神经元的神经营养因子，三叉神经和背根神经节中的GFR α 2表达细胞也在NTN-/-小鼠中耗尽。表达GFR α 2的神经元的丧失，结合早期的研究，为GFR α 2/Ret受体复合物作为体内NTN功能的关键介质提供了强有力的支持。
Neurturin (NTN) is a neuronal survival factor that activates the Ret tyrosine kinase in the presence of a GPI-linked coreceptor (either GFR alpha 1 or GFR alpha 2). Neurturin-deficient (NTN-/-) mice generated by homologous recombination are viable and fertile but have defects in the enteric nervous system, including reduced myenteric plexus innervation density and reduced gastrointestinal motility. Parasympathetic innervation of the lacrimal and submandibular salivary gland is dramatically reduced in NTN-/- mice, indicating that Neurturin is a neurotrophic factor for parasympathetic neurons, GFR alpha 2-expressing cells in the trigeminal and dorsal root ganglia are also depleted in NTN-/- mice. The loss of GFR alpha 2-expressing neurons, in conjunction with earlier studies, provides strong support for GFR alpha 2/Ret receptor complexes as the critical mediators of NTN function in vivo.