SEVERE SENSORY AND SYMPATHETIC NEUROPATHIES IN MICE CARRYING A DISRUPTED TRK/NGF RECEPTOR GENE
SEVERE SENSORY AND SYMPATHETIC NEUROPATHIES IN MICE CARRYING A DISRUPTED TRK/NGF RECEPTOR GENE
复制标题
DOI：
10.1038/368246a0
复制
发表时间：
1994-03-17
期刊：
影响因子：
64.8
通讯作者：
BARBACID, M
中科院分区：
文献类型：
--
作者：
SMEYNE, RJ;KLEIN, R;BARBACID, M
神经生长因子（NGF）诱导神经突生长，并促进培养的胚胎感觉和交感神经元的存活（1，2）。在体内，NGF降低交感神经节发育中自然发生的细胞死亡程度，并保护基底前脑和尾壳核的胆碱能神经元（1-3）。NGF与低亲和力p75受体和Trk相互作用，Trk是一种由trk原癌基因编码的受体酪氨酸激酶（4，5）。为了研究Trk在体内的作用，我们通过同源重组在胚胎干细胞中切除了该基因。缺乏Trk的小鼠具有严重的感觉和交感神经病变，并且大多数在出生后一个月内死亡。它们在三叉神经、交感神经和背根神经节中有广泛的神经元细胞损失，以及胆碱能基底前脑向海马和皮质的投射减少。这些研究结果表明，Trk是NGF在体内的营养作用的主要介质，并且这种信号传导途径在外周和中枢神经系统的发育中起着至关重要的作用。
NERVE growth factor (NGF) induces neurite outgrowth and promotes survival of embryonic sensory and sympathetic neurons in culture(1,2). In vivo, NGF decreases the extent of naturally occurring cell death in developing sympathetic ganglia and protects cholinergic neurons of the basal forebrain and caudatoputamen(1-3). NGF interacts with the low-affinity p75 receptor and with Trk, a receptor tyrosine kinase encoded by the trk proto-oncogene(4,5). To study the role of Trk in vivo, we have ablated the gene in embryonic stem cells by homologous recombination. Mice lacking Trk have severe sensory and sympathetic neuropathies and most die within one month of birth. They have extensive neuronal cell loss in trigeminal, sympathetic and dorsal root ganglia, as well as a decrease in the cholinergic basal forebrain projections to the hippocampus and cortex. These findings demonstrate that Trk is the primary mediator of the trophic actions of NGF in vivo and that this signalling pathway plays a crucial role in the development of both the peripheral and the central nervous systems.