Aberrant responses to acoustic stimuli in mice deficient for neural recognition molecule NB-2
Aberrant responses to acoustic stimuli in mice deficient for neural recognition molecule NB-2
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DOI：
10.1046/j.1460-9568.2003.02514.x
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发表时间：
2003-03-01
影响因子：
3.4
通讯作者：
Watanabe, K
中科院分区：
文献类型：
--
作者：
Li, H;Takeda, Y;Watanabe, K
Nb-2是免疫球蛋白超家族中接触蛋白亚群的一员，在出生后神经系统中特异表达，在出生后3周达到最高水平。NB-2在体外具有促进轴突生长的活性。为了评估它在神经系统中的功能，我们产生了突变的小鼠，在其中，NB-2基因的一部分被去除，并被tau-lacZ基因取代。Nb-2缺陷小鼠的大体形态和大体解剖特征正常。杂合子小鼠的LacZ表达模式表明，NB-2优先在中枢听觉通路中表达。在听源性惊厥试验中，Nb-2基因缺陷小鼠表现出较低的野跑发生率，但死亡率高于野生型小鼠。C-Fos免疫组织化学结果显示，Nb-2基因缺陷小鼠听源性惊厥诱发的神经兴奋性在下丘背侧皮质和外皮质均明显减弱，而野生型小鼠的神经兴奋性明显增强。作为对启动后纯音刺激的反应，Nb-2缺陷小鼠在下丘中央核表现出弥漫性的低水平c-Fos表达，这与野生型小鼠的紧张性图谱所对应的条带状c-Fos表达明显不同。综上所述，这些结果表明，NB-2的缺乏会导致听觉系统中神经元活动的损害。
NB-2, a member of the contactin subgroup in the immunoglobulin superfamily, is expressed specifically in the postnatal nervous system, reaching a maximum level at 3 weeks postnatal. NB-2 displays neurite outgrowth-promoting activity in vitro. To assess its function in the nervous system, we generated mutant mice in which a part of the NB-2 gene was ablated and replaced with the tau-LacZ gene. The general appearance of NB-2-deficient mice and their 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 test, NB-2-deficient mice exhibited a lower incidence of wild running, but a higher mortality rate than the wild-type littermates. c-Fos immunohistochemistry demonstrated that neural excitability induced by the audiogenic seizure test in the NB-2-deficient mice was prominently attenuated in both the dorsal and external cortices of the inferior colliculus, where enhanced neural excitability was observed in the wild-type mice. In response to pure-tone stimulation after priming, NB-2-deficient mice exhibited a diffuse and low level of c-Fos expression in the central nucleus of the inferior colliculus, which was distinctly different from the band-like c-Fos expression corresponding to the tonotopic map in the wild-type littermates. Taken together, these results suggest that a lack of NB-2 causes impairment of the neuronal activity in the auditory system.