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Rosa26ノックイン型タウオパチー認知症モデルマウスの作出

https://repo.qst.go.jp/records/85015
https://repo.qst.go.jp/records/85015
f798f83e-0cce-4af7-94e3-68099beaa89e
Item type 会議発表用資料 / Presentation(1)
公開日 2022-02-25
タイトル
タイトル Rosa26ノックイン型タウオパチー認知症モデルマウスの作出
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言語 jpn
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資源タイプ識別子 http://purl.org/coar/resource_type/c_c94f
資源タイプ conference object
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アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
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Rin, Yanai

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WEKO 1025256

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内容記述タイプ Abstract
内容記述 Tauopathy is characterized by the fibrillar tau accumulation in central nervous system. Neurofibrillary lesions strongly correlated with cognitive deficits in neurodegenerative diseases. Animal models of tauopathy are essential for preclinical studies of Alzheimer’s disease and related dementias. Overexpression of familial mutant tau has been utilized to drive tauopathy and disease-relevant phenotypes in a number of different animal models that have established a role of this protein in neurodegeneration. The rTg4510mouse line is one of the popular tauopathy models (Santacruz et al. 2005). This model uniquely employed the CaMKIIa promoter-driven tetracycline transactivator (tTA) transgene to drive 0N4R P301L tau expression in the forebrain and to allow conditional repression of the transgenic tau expression through the use of doxycycline, tetracycline analog. Recent studies revealed that transgenic insertion/deletion mutations may affect pathogenesis of tauopathy in the rTg4510 mice (Gamache et al. 2019). To overcome this issue, we generate a novel tauopathy mouse model, in which 1N4R P301L human tau was integrated in the Rosa26 safe harbor gene and expressed by cross-breeding with tTA mice under C57BL/6J background. Successfully, this Rosa26-KI tau mouse expresses P301L human tau in the forebrain with ~4-fold of mouse tau. A homozygous mouse for P301L human tau gene developed pretangle pathology in hippocampus at 13 months of age. Although this model delayed tau pathology to compare with rTg4510 mice, either leaky expression of P301L human tau or dentate granule neuron degeneration was absent in this model. Further characterizations are ongoing for the usage of preclinical examinations.
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内容記述タイプ Other
内容記述 第64回日本神経化学大会
発表年月日
日付 2021-09-30
日付タイプ Issued
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