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

GPI锚定神经粘附分子NB-2基因敲除小鼠的生成和功能分析。

• 批准号: 13680858
• 负责人: TAKEDA Yasuo
• 金额: $ 2.3万
• 依托单位: TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680858/
• 关键词: Cell Adehesion Molecule; GPI-Anchored Protein; NB-2; Auditory System; Knockout Mice

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.

NB-2是免疫球蛋白超家族中接触蛋白亚组的成员，在神经系统中限制性表达，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NB-2基因的一部分来产生突变小鼠。NB-2缺陷小鼠的一般外观和大体解剖特征是正常的。在杂合子小鼠中的LacZ表达模式揭示NB-2优先在中枢听觉通路中表达。在听源性癫痫发作易感性（AGS）试验中，NB-2突变小鼠表现出较低的野生型小鼠奔跑的发生率，但较高的死亡率比野生型小鼠。c-Fos表达表明，在NB-2缺陷型小鼠中由AGS诱导的神经活性在下丘的背侧和外部皮质中显著减弱，其中在野生型小鼠中观察到增强的神经活性。纯音刺激后引发，NB-2缺陷型小鼠表现出扩散和低水平的c-Fos的表达在下丘中央核相比，在野生型同窝小鼠的c-Fos的强烈和tonotopic带的表达。总之，这些结果表明，NB-2的缺乏损害了听觉系统中的神经元活动。

项目成果

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