Generation and Functional Analysis for GPI-anchored neural adhesion molecule NB-2 gene knockout mice.

NB-2是免疫球蛋白超家族中接触蛋白亚群的成员，在神经系统中有限制性表达，在出生后3周达到最高水平。NB-2在体外表现出促进神经突生长的活性。为了评估其在神经系统中的功能，我们通过用tau-LacZ基因替换部分NB-2基因来产生突变小鼠。NB-2缺陷小鼠总体外观及大体解剖特征均正常。LacZ在杂合小鼠中的表达模式显示NB-2优先表达于中枢听觉通路。在听原性癫痫易感性（AGS）试验中，NB-2突变小鼠的野跑发生率较低，但死亡率高于野鼠。c-Fos的表达表明，在NB-2缺陷小鼠中，AGS诱导的下丘背皮层和外皮层的神经活动明显减弱，而在野生型小鼠中，神经活动增强。在启动后的纯音刺激下，NB-2缺陷小鼠的下丘中央核中c-Fos的表达呈弥漫性和低水平表达，而野生型小鼠的c-Fos则呈强的张力带状表达。综上所述，这些结果表明缺乏NB-2会损害听觉系统中的神经元活动。

NB-2, a member of the contactin subgroup in the immunoglobulin superfamily, is restrictively expressed in the nervous system, reaching the maximum level at postnatal 3 weeks. NB-2 displays neurite outgrowth-promoting activity in vitro. To assess its function in the nervous system, we generated mutant mice ablating a part of NB-2 gene by replacing with the tau-LacZ gene. The general appearance of NB-2 deficient mice and the gross anatomical features were normal. The LacZ expression patterns in heterozygous mice revealed that NB-2 is preferentially expressed in the central auditory pathways. In the audiogenic seizure susceptibility (AGS) test, NB-2 mutant mice exhibited lower incidence of wild running, but higher rate of mortality than the wild-type littermates. c-Fos expression demonstrated that neural activity induced by the AGS in the NB-2 deficient mice was prominently attenuated in the both dorsal and external cortexes of inferior colliculus where enhanced neural activity is observed in the wild-type mice. Pure-tone stimulation after priming, NB-2 deficient mice exhibited a diffusive and low level of c-Fos expression in the central nucleus of inferior colliculus in comparison with a strong and a tonotopic banding expression of c-Fos in the wild-type littermates. Taken together, these results suggest that lack of NB-2 impairs the neuronal activity in the auditory system.