Studies on Brain Histamine Neurons Using Gene-Targetted Mice

使用基因靶向小鼠进行脑组胺神经元研究

• 批准号: 10044229
• 负责人: WATANABE Takehiko
• 金额: $ 9.79万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10044229/
• 关键词: Histamine; H1 receptor; H2 receptor; Histidine decarboxylase; Knock-out mice; Brain functions; 遺伝子改変動物; H_1受容体; H_2受容体; ヒスタミンN-メチル基転移酵素; 脳機能

The histaminergic neuron system in the brain attracts interests of many neuroscientists, because it is related to various brain functions. Recently, mice with genes for H1 and H2 receptors and histidine decarboxylase (HDC, a histamine-forming enzyme) knocked out have been developed. In this research, international collaboration of functions of histamime in sleep-awakeness circadian rhythm, spontaneous behavior, anxiety, learning-memory and convulsions have been carried out. So far, it turned out that HDC-KO mice have a little level of histamine in spite of no HDC activity, suggesting that there is another source of histamine. We speculate that histamine is absorbed from the gut, because feeding the KO mice with a diet of low histamine content decreased the histamine levels in tissues. For easy and reliable comparison of data obtained in wild and KO mice, the inbred 129 mice were produced. By the two reqasons mentioned above, the distribution of the mice was delayed but they are now being sent to the collaborators. From November 22 to 25, 2000, International Sendai Histamine Symposium was held in Sendai, and all the members of this grant attended the Sympo sium and exchanged informations and ideas.

脑内的组胺能神经元系统由于与脑的多种功能有关而引起了神经科学家的兴趣。最近，已经开发出了H1和H2受体基因和组氨酸脱羧酶（HDC，一种组胺形成酶）基因被敲除的小鼠。本研究开展了组胺在睡眠-觉醒昼夜节律、自发行为、焦虑、学习记忆和惊厥中的作用的国际合作。到目前为止，事实证明，尽管没有HDC活性，但HDC-KO小鼠具有少量组胺水平，这表明存在另一种组胺来源。我们推测组胺是从肠道吸收的，因为给KO小鼠喂食低组胺含量的饮食会降低组织中的组胺水平。为了容易和可靠地比较野生和KO小鼠中获得的数据，产生了近交系129只小鼠。由于上述两个原因，小鼠的分配被推迟，但它们现在被送到合作者那里。2000年11月22日至25日，国际仙台组胺研讨会在仙台举行，本基金会全体成员参加了会议，并交流了信息和意见。

项目成果

M.Izumiyama et al: "Lack of the temperature-induced polypnea in hsitamine H1 receptro deficient mice."Neurosci.Lett.. 284. 139-142 (2000)

M.Izumiyama 等人：“组胺 H1 受体缺陷小鼠中缺乏温度诱导的呼吸急促。”Neurosci.Lett.. 284. 139-142 (2000)

H.Toyota: "Histamine H1 receptor binding capacities in the amgdalin of the amgdala of the amy***kinding rat"J.Neurochem. 72. 2177-2180 (1999)

H.Toyota：“amy***kinding 大鼠杏仁核中的组胺 H1 受体结合能力”J.Neurochem。

K.Yanai et al: "Behavioral characterization and amouts of brain monoamines and their metabolites in mice lacking histamine H1 receptors."Neuroscience. 87. 479-487 (1998)

K.Yanai 等人：“缺乏组胺 H1 受体的小鼠的行为特征和脑单胺及其代谢物的数量。”神经科学。

H.Nakahara et al: "Vascular permeability in allergic conjunctivitis in mice lacking histamine H1 receptors."Eur.J.Pharmacol.. (In press). (2000)

H.Nakahara 等人：“缺乏组胺 H1 受体的小鼠过敏性结膜炎的血管通透性。”Eur.J.Pharmacol..（正在出版）。

K.Maeyama et al: "Hisatamine"Progress in HPLC-HPCE, VSP, Utrecht. Vol.7. 64 (1998)

K.Maeyama 等人：“Hisatamine”HPLC-HPCE 进展，VSP，乌得勒支。