Generation of a new transgenic mouse model for assessment of tau gene silencing therapies.
Generation of a new transgenic mouse model for assessment of tau gene silencing therapies.
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DOI：
10.1186/s13195-016-0202-1
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发表时间：
2016-09-05
期刊：
影响因子：
--
通讯作者：
Borchelt DR
中科院分区：
文献类型：
--
作者：
Fromholt S;Reitano C;Brown H;Lewis J;Borchelt DR
Targeting the expression of genes has emerged as a potentially viable therapeutic approach to human disease. In Alzheimer’s disease, therapies that silence the expression of tau could be a viable strategy to slow disease progression. We produced a novel strain of transgenic mice that could be used to assess the efficacy of gene knockdown therapies for human tau, in live mice. We designed a tetracycline-regulated transgene construct in which the cDNA for human tau was fused to ubiquitin and to luciferase to create a single fusion polyprotein, termed TUL. When expressed in brain, the TUL polyprotein was cleaved by ubiquitin-processing enzymes to release the luciferase as an independent protein, separating the half-life of luciferase from the long-lived tau protein. Treatment of bigenic tTA/TUL mice with doxycycline produced rapid declines in luciferase levels visualized by in vivo imaging and ex vivo enzyme measurement. This new mouse model can be used as a discovery tool in optimizing gene targeting therapeutics directed to reduce human tau mRNA levels.
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DOI：
10.1098/rstb.2013.0144
发表时间：
2014-01-05
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Kimura T;Whitcomb DJ;Jo J;Regan P;Piers T;Heo S;Brown C;Hashikawa T;Murayama M;Seok H;Sotiropoulos I;Kim E;Collingridge GL;Takashima A;Cho K
通讯作者：
Cho K
DOI：
10.1007/s12031-011-9589-0
发表时间：
2011-11
期刊：
Journal of molecular neuroscience : MN
影响因子：
--
作者：
Dickson DW;Kouri N;Murray ME;Josephs KA
通讯作者：
Josephs KA
影响因子：
5.3
作者：
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通讯作者：
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影响因子：
3.5
作者：
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影响因子：
12.4
作者：
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通讯作者：
Mandel, RJ