Cloning and characterization of a novel neuropeptide using TRH knockout mice.

使用 TRH 敲除小鼠克隆和表征新型神经肽。

• 批准号: 14571060
• 负责人: YAMADA Masanobu
• 金额: $ 2.11万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571060/
• 关键词: TRH; knockout mouse; neurophysiological action; MDP1; ノックアウトマウス; 神経ペプチド

TRH has been reported to possess several neurophysiological actions in the brain. To gain insights into the molecular mechanisms underlying these effects, we attempted to clone a cDNA that was regulated by TRH using TRH knockout mice and subtractive cDNA analysis and a microarray system. Over 100 clones obtained by these analyses between the wild-type and TRH^<-/-> cerebellum were analyzed. Among them, a clone, mDP1 mRNA level in the euthyroid TRH^<-/-> cerebellum supplemented with thyroid hormone were significantly decreased compared with those in the wild-type. Northern blot analysis of seven brain regions including hypothalamus, striatum, midbrain hippocampus, pons, cerebellum, and cortex revealed that mDP1 mRNA were expressed significantly in the hypothalamus and cerebellum. Furthermore, starvation for 72 hours lead to a significant decrease in mDP1 mRNA level in the hypothalamus and cerebellum. These results suggested that mDP1 might be a substance for regulating satiety behavior.

据报道，TRH 在大脑中具有多种神经生理作用。为了深入了解这些效应背后的分子机制，我们尝试使用 TRH 敲除小鼠、消减 cDNA 分析和微阵列系统来克隆受 TRH 调节的 cDNA。对通过这些分析在野生型和TRH^-/-小脑之间获得的100多个克隆进行了分析。其中，补充甲状腺激素的克隆，甲状腺功能正常的TRH^-/->小脑中mDP1 mRNA水平与野生型相比显着降低。对下丘脑、纹状体、中脑海马、脑桥、小脑和皮质等七个脑区的 Northern blot 分析显示，mDP1 mRNA 在下丘脑和小脑中显着表达。此外，饥饿72小时会导致下丘脑和小脑中mDP1 mRNA水平显着降低。这些结果表明mDP1可能是调节饱腹感行为的物质。

项目成果

A novel TRH-PFTAIRE protein kinase 1 pathway in the cerebellum : subtractive hybridization analysis of TRH-deficient mice.

小脑中一种新的 TRH-PFTAIRE 蛋白激酶 1 通路：TRH 缺陷小鼠的消减杂交分析。

• 发表时间: 2002
• 期刊: Endocrinology 143(7)
• 作者: Kajiwara A;Kurehara H;Kitaguch K;Furuya H;Morimoto Y;Kirita T;Fukuda K;Takahashi Y.;Hashida T.
• 通讯作者: Hashida T.