Heuckeroth R O, Enomoto H, Grider J R, Golden J P, Hanke J A, Jackman A, Molliver D C, Bardgett M E, Snider W D, Johnson E M, Milbrandt J
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Neuron. 1999 Feb;22(2):253-63. doi: 10.1016/s0896-6273(00)81087-9.
Neurturin (NTN) is a neuronal survival factor that activates the Ret tyrosine kinase in the presence of a GPI-linked coreceptor (either GFR alpha1 or GFR alpha2). 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 alpha2-expressing cells in the trigeminal and dorsal root ganglia are also depleted in NTN-/- mice. The loss of GFR alpha2-expressing neurons, in conjunction with earlier studies, provides strong support for GFR alpha2/Ret receptor complexes as the critical mediators of NTN function in vivo.
神经营养因子（NTN）是一种神经元存活因子，在存在糖基磷脂酰肌醇（GPI）连接的共受体（GFRα1或GFRα2）的情况下可激活Ret酪氨酸激酶。通过同源重组产生的神经营养因子缺陷（NTN-/-）小鼠是存活且可育的，但在肠神经系统中存在缺陷，包括肌间神经丛神经支配密度降低和胃肠蠕动减弱。NTN-/-小鼠泪腺和下颌下唾液腺的副交感神经支配显著减少，这表明神经营养因子是副交感神经元的神经营养因子。三叉神经节和背根神经节中表达GFRα2的细胞在NTN-/-小鼠中也减少。表达GFRα2的神经元的缺失，结合早期研究，为GFRα2/Ret受体复合物作为NTN在体内功能的关键介质提供了有力支持。
