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Ethanol Sensitivity of Fyn-deficient mice

Fyn 缺陷小鼠的乙醇敏感性

基本信息

批准号：
09410023
负责人：
NIKI Hiroaki
金额：
$ 6.85万
依托单位：
The Institute of Physical and Chemical Research (RIKEN)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09410023/
关键词：
Fyn-tyrosine kinase Ethanol sensitivity Mutant mice NMDA receptor Rightin reflex Tyrosine phosphorylation Gene targeting Western blotting Fynチロシンキナーゼ

项目摘要

Animals vary in their sensitivity to ethanol (EtOH), a trait at least partly determined by genetic factors. To identify possible responsible genes, mice lacking Fyn, a non-receptor type tyrosine kinase, were investigated. Fyn-deficient mice were hypersensitive to the hypnotic effect of EtOH as measured by the duration of loss of righting reflex. The hypersensitivity is specific to EtOH since no significant differences were found in the duration of loss of righting reflex induced by flurazepam (a benzodiazepine derivative). Analysis of the blood EtOH concentration revealed no differences between Fyn-deficient and control mice. Thus, lack of Fyn tyrosine kinase exacerbates the hypnotic effects of EtOH.The administration of EtOH enhanced tyrosine phosphorylation of the NMDA receptor (NMDAR) in the hippocampus of control mice, but not of Fyn deficient mice.The inhibition of NMDAR-mediated EPSPs by EtOH is known to be gradually reduced during EtOH exposure in slice experiment (acute tolerance). Acute tolerance to EtOH inhibition of NMDAR-mediated EPSPs in hippocampal slices developed in control mice, but not in Fyn-deficient mice. These results indicate that Fyn affects behavioral, biochemical, and physiological responses to EtOH.

动物对乙醇(Etoh)的敏感性不同，这一特征至少部分由遗传因素决定。为了确定可能的相关基因，研究了缺乏Fyn的小鼠，Fyn是一种非受体类型的酪氨酸激酶。Fyn缺陷小鼠对乙醇的催眠作用非常敏感，通过翻正反射丧失的持续时间来衡量。这种超敏反应是乙醇所特有的，因为在氟西潘(一种苯二氮类化合物)引起的翻正反射丧失的持续时间方面没有发现明显的差异。对血液中乙醇浓度的分析表明，Fyn缺陷小鼠和对照小鼠之间没有差异。因此，缺乏Fyn酪氨酸激酶加剧了EtOh的催眠作用。给予Etoh可增强对照组小鼠海马区NMDAR的酪氨酸磷酸化，但不能增加Fyn缺乏小鼠的NMDAR酪氨酸磷酸化。已知在切片实验中，Etoh对NMDAR介导的EPSPS的抑制逐渐减少。NMDAR介导的EPSP在对照组小鼠海马片中对乙醇抑制的急性耐受性在对照组小鼠中发展，但在Fyn缺陷小鼠中不出现。这些结果表明，Fyn影响对乙醇的行为、生化和生理反应。