A study of transgenic mice with reduced calbindin-D28K expression

钙结合蛋白-D28K 表达减少的转基因小鼠的研究

• 批准号: 08671108
• 负责人: TAKAHASHI Tadashi
• 金额: $ 1.47万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671108/
• 关键词: calcium binding protein; calbindin; transgenic mice; antisense RNA; in situ hybridization; immunohistochemistry; Alzheimer-type dementia; parvalbumin; トランスジェニックマウス; in situ ハイブリダイゼーション; アンチセンス遺伝子導入; メッセンジャーRNA

In situ hybridization and immunohistochemical studies showed that this antisense construct abolishes calbindin (GB) mRNA and protein expression in the forebrain and midbrain of the transgenic (Tg) mice in a dose dependent manner. It is interesting to .note that the sense hybridiza-tion signal was dramatically reduced in cerebellar Purkinje cells (approximately -10%) which express the highest levels of GB mRNA and protein. Other histochemical and quantitative analysis (HE, Nissi, Holzer and KB stain) of old mice(postnatal 24 months) tissue sections indicated that there were no gross abnormalities or cell loss in any of the forebrain structures. On the other hand, learning and memory capacities have been assesed. Homozygous mice were significantly worse at reaching an asymptote of working level performance than control mice. We have also indicated that a dramatic decrease in hippocampal (CAl) long-term potentiation in the Tg mice. These Tg mice may be valuable in the study of learning and memory mechanism including some of ATD pathology.

原位杂交和免疫组织化学研究表明，这种反义构建体以剂量依赖性方式消除了转基因（Tg）小鼠前脑和中脑中钙结合蛋白（GB）mRNA和蛋白的表达。有趣的是，在表达最高水平的 GB mRNA 和蛋白质的小脑浦肯野细胞中，有义杂交信号显着降低（约-10%）。对年老小鼠（出生后 24 个月）组织切片的其他组织化学和定量分析（HE、Nissi、Holzer 和 KB 染色）表明，任何前脑结构均没有明显异常或细胞丢失。另一方面，评估了学习和记忆能力。纯合子小鼠在达到工作水平表现的渐近线方面明显比对照小鼠差。我们还表明，Tg 小鼠的海马 (CA1) 长期增强作用显着下降。这些 Tg 小鼠可能在学习和记忆机制（包括一些 ATD 病理学）的研究中有价值。

项目成果

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Hirai Arai：“阿尔茨海默病的病理学”《老年精神病学杂志》9. 434-439 (1998)。

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Iwamoto N：“阿尔茨海默病患者大脑白质中淀粉样沉积物的分布；与血管的关系。”

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Iwamoto N、Nishiyama E、Ohwada J、Arai H：“淀粉样蛋白沉积物在阿尔茨海默病大脑白质中的分布；与血管的关系。”

T.Takahashi: "Amalysis of fransgenic mice with reduced calbindin-D28k expression : Neuropathological,neurophysiological and behavioral studieg." Psychiatry and Clinical Neurosciences. 51・1. S7 (1997)

T.Takahashi：“钙结合蛋白-D28k 表达减少的转基因小鼠的分析：神经病理学、神经生理学和行为研究。”精神病学和临床神经科学 51·1。