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A novel transgenic mouse line with hippocampus-dominant and inducible expression of truncated human tau

BACKGROUND: Intraneuronal accumulation of hyperphosphorylated tau is a defining hallmark of Alzheimer’s disease (AD). However, mouse models imitating AD-exclusive neuronal tau pathologies are lacking. METHODS: We generated a new tet-on transgenic mouse model expressing truncated human tau N1-368 (te...

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Autores principales: Gao, Yang, Wang, Yuying, Lei, Huiyang, Xu, Zhendong, Li, Shihong, Yu, Haitao, Xie, Jiazhao, Zhang, Zhentao, Liu, Gongping, Zhang, Yao, Zheng, Jie, Wang, Jian-Zhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637005/
https://www.ncbi.nlm.nih.gov/pubmed/37950283
http://dx.doi.org/10.1186/s40035-023-00379-5
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author Gao, Yang
Wang, Yuying
Lei, Huiyang
Xu, Zhendong
Li, Shihong
Yu, Haitao
Xie, Jiazhao
Zhang, Zhentao
Liu, Gongping
Zhang, Yao
Zheng, Jie
Wang, Jian-Zhi
author_facet Gao, Yang
Wang, Yuying
Lei, Huiyang
Xu, Zhendong
Li, Shihong
Yu, Haitao
Xie, Jiazhao
Zhang, Zhentao
Liu, Gongping
Zhang, Yao
Zheng, Jie
Wang, Jian-Zhi
author_sort Gao, Yang
collection PubMed
description BACKGROUND: Intraneuronal accumulation of hyperphosphorylated tau is a defining hallmark of Alzheimer’s disease (AD). However, mouse models imitating AD-exclusive neuronal tau pathologies are lacking. METHODS: We generated a new tet-on transgenic mouse model expressing truncated human tau N1-368 (termed hTau368), a tau fragment increased in the brains of AD patients and aged mouse brains. Doxycycline (dox) was administered in drinking water to induce hTau368 expression. Immunostaining and Western blotting were performed to measure the tau level. RNA sequencing was performed to evaluate gene expression, and several behavioral tests were conducted to evaluate mouse cognitive functions, emotion and locomotion. RESULTS: Dox treatment for 1–2 months at a young age induced overt and reversible human tau accumulation in the brains of hTau368 transgenic mice, predominantly in the hippocampus. Meanwhile, the transgenic mice exhibited AD-like high level of tau phosphorylation, glial activation, loss of mature neurons, impaired hippocampal neurogenesis, synaptic degeneration and cognitive deficits. CONCLUSIONS: This study developed a well-characterized and easy-to-use tool for the investigations and drug development for AD and other tauopathies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40035-023-00379-5.
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spelling pubmed-106370052023-11-11 A novel transgenic mouse line with hippocampus-dominant and inducible expression of truncated human tau Gao, Yang Wang, Yuying Lei, Huiyang Xu, Zhendong Li, Shihong Yu, Haitao Xie, Jiazhao Zhang, Zhentao Liu, Gongping Zhang, Yao Zheng, Jie Wang, Jian-Zhi Transl Neurodegener Research BACKGROUND: Intraneuronal accumulation of hyperphosphorylated tau is a defining hallmark of Alzheimer’s disease (AD). However, mouse models imitating AD-exclusive neuronal tau pathologies are lacking. METHODS: We generated a new tet-on transgenic mouse model expressing truncated human tau N1-368 (termed hTau368), a tau fragment increased in the brains of AD patients and aged mouse brains. Doxycycline (dox) was administered in drinking water to induce hTau368 expression. Immunostaining and Western blotting were performed to measure the tau level. RNA sequencing was performed to evaluate gene expression, and several behavioral tests were conducted to evaluate mouse cognitive functions, emotion and locomotion. RESULTS: Dox treatment for 1–2 months at a young age induced overt and reversible human tau accumulation in the brains of hTau368 transgenic mice, predominantly in the hippocampus. Meanwhile, the transgenic mice exhibited AD-like high level of tau phosphorylation, glial activation, loss of mature neurons, impaired hippocampal neurogenesis, synaptic degeneration and cognitive deficits. CONCLUSIONS: This study developed a well-characterized and easy-to-use tool for the investigations and drug development for AD and other tauopathies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40035-023-00379-5. BioMed Central 2023-11-10 /pmc/articles/PMC10637005/ /pubmed/37950283 http://dx.doi.org/10.1186/s40035-023-00379-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Gao, Yang
Wang, Yuying
Lei, Huiyang
Xu, Zhendong
Li, Shihong
Yu, Haitao
Xie, Jiazhao
Zhang, Zhentao
Liu, Gongping
Zhang, Yao
Zheng, Jie
Wang, Jian-Zhi
A novel transgenic mouse line with hippocampus-dominant and inducible expression of truncated human tau
title A novel transgenic mouse line with hippocampus-dominant and inducible expression of truncated human tau
title_full A novel transgenic mouse line with hippocampus-dominant and inducible expression of truncated human tau
title_fullStr A novel transgenic mouse line with hippocampus-dominant and inducible expression of truncated human tau
title_full_unstemmed A novel transgenic mouse line with hippocampus-dominant and inducible expression of truncated human tau
title_short A novel transgenic mouse line with hippocampus-dominant and inducible expression of truncated human tau
title_sort novel transgenic mouse line with hippocampus-dominant and inducible expression of truncated human tau
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637005/
https://www.ncbi.nlm.nih.gov/pubmed/37950283
http://dx.doi.org/10.1186/s40035-023-00379-5
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