Crowley C, Spencer S D, Nishimura M C, Chen K S, Pitts-Meek S, Armanini M P, Ling L H, McMahon S B, Shelton D L, Levinson A D
Department of Cell Genetics, Genentech, Incorporated, South San Francisco, California 94080.
Cell. 1994 Mar 25;76(6):1001-11. doi: 10.1016/0092-8674(94)90378-6.
Homologous recombination was utilized to generate mice with a deletion in the coding sequence of the nerve growth factor (NGF) gene. Animals homozygous for NGF disruption failed to respond to noxious mechanical stimuli, and histological analysis revealed profound cell loss in both sensory and sympathetic ganglia. Within dorsal root ganglia, effects of the mutation appeared to be restricted to small and medium peptidergic neurons. These observations confirm the critical dependence of sensory and sympathetic neurons on NGF and demonstrate that other neurotrophins are not able to compensate for the loss of NGF action on these cells. Examination of the central nervous system revealed that, in marked contrast with neurons of sensory and sympathetic ganglia, basal forebrain cholinergic neurons differentiate and continue to express phenotypic markers for the life span of the null mutant mice. Thus, differentiation and initial survival of central NGF-responsive neurons can occur in the absence of NGF.
利用同源重组技术培育出神经生长因子（NGF）基因编码序列缺失的小鼠。NGF基因敲除纯合子动物对有害机械刺激无反应，组织学分析显示感觉神经节和交感神经节均有严重的细胞丢失。在背根神经节内，突变的影响似乎仅限于中小肽能神经元。这些观察结果证实了感觉神经元和交感神经元对NGF的关键依赖性，并表明其他神经营养因子无法补偿NGF对这些细胞作用的丧失。对中枢神经系统的检查发现，与感觉神经节和交感神经节的神经元形成鲜明对比的是，基底前脑胆碱能神经元在无效突变小鼠的寿命期间分化并继续表达表型标志物。因此，中枢NGF反应性神经元的分化和初始存活可以在没有NGF的情况下发生。
