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，达到产后3周的最大水平。 NB-2在体外显示神经突生长促进活性。为了评估其在神经系统中的功能，我们通过用tau-lacz基因替换来消除NB-2基因的一部分突变小鼠。 NB-2缺乏小鼠和总解剖特征的一般外观是正常的。杂合小鼠中的LACZ表达模式表明，NB-2优先在中央听觉途径中表达。在听觉性癫痫发作易感性（AGS）测试中，NB-2突变小鼠的野生跑步率较低，但死亡率较高，而死亡率较高。 C-FOS表达表明，在NB-2缺乏小鼠中AG诱导的神经活性在下丘丘的背侧和外皮层中显着减弱，在野生型小鼠中观察到了增强的神经活性。启动后的纯音刺激，NB-2缺乏小鼠在下丘中心核中表现出扩散且低水平的C-FOS表达，与野生型垃圾群中C-FOS的强和调子谱带表达相比。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性。

项目成果

Takeda, Y., Notsu, T., Uyemura, K.et al.: "Functional analysis for peripheral myalin protein PASII/PMP22: Is it a member of claudin superfamily?"Neurochem. Res.. 26. 599-607 (2001)

Takeda, Y.、Notsu, T.、Uyemura, K.等人：“外周髓磷脂蛋白 PASII/PMP22 的功能分析：它是密蛋白超家族的成员吗？”Neurochem。

Takeda, Y., Murakami, Y., Uyemura, K.et al.: "The roles of cell adhesion molecules on the formation of peripheral I-u myelin."Keio J. Medicine. 50. 240-248 (2001)

Takeda, Y.、Murakami, Y.、Uyemura, K.等人：“细胞粘附分子对外周 I-u 髓磷脂形成的作用。”Keio J. Medicine。

Takeda, Y., Akasaka, K., Watanabe, K. et al.: "Impaired motor coordination in mice lacking neural recognition molecule NB-3 of the contactin/F3 subgroup"Journal of Neurobiology. In press. (2003)

Takeda, Y.、Akasaka, K.、Watanabe, K. 等人：“缺乏 contactin/F3 亚组的神经识别分子 NB-3 的小鼠运动协调受损”神经生物学杂志。

Nagata, S., Saito, R., Watanabe, K.et al.: "Multiple variants of receptor-type protein tyrosine phosphatase b are expressed in the central nervous system of Xenopus."Gene. 262. 81-88 (2001)

Nagata, S.、Saito, R.、Watanabe, K.等人：“受体型蛋白酪氨酸磷酸酶 b 的多种变体在非洲爪蟾的中枢神经系统中表达。”基因。