Evidence map›Paper›PMID 27593210›Full record

ArticleAlzheimer's research & therapy2016

Generation of a new transgenic mouse model for assessment of tau gene silencing therapies.

Susan Fromholt, Christian Reitano, Hilda Brown, Jada Lewis, David R Borchelt

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.2field-weighted citation impact, top 38% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Susan FromholtDepartment of Neuroscience, Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA.
Christian ReitanoDepartment of Neuroscience, Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA.
Hilda BrownDepartment of Neuroscience, Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA.
Jada LewisDepartment of Neuroscience, Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA. jada.lewis@ufl.edu.
David R BorcheltDepartment of Neuroscience, Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA. drb1@ufl.edu.
University of Florida · US

Funding

New Models to Assay Gene Silencing TherapiesR21NS077032 · NINDS · UNIVERSITY OF FLORIDA · PI BORCHELT, DAVID R, LEWIS, JADA M · 2011 to 2012
$403k
NINDS NIH HHS R21 NS077032
6 · The paper itself

Abstract

backgroundTargeting 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.

methodsWe 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.

resultsWhen 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.

conclusionsThis new mouse model can be used as a discovery tool in optimizing gene targeting therapeutics directed to reduce human tau mRNA levels.

Indexed as

Disease Models, AnimalGene SilencingGenetic TherapyAnimalsBrainDoxycyclineHumansLuciferasesMice, TransgenicRNA, MessengerTauopathiestau ProteinsTetracyclineUbiquitinDoxycyclineLuciferasesMAPT protein, humanRNA, Messengertau ProteinsTetracyclineUbiquitinAlzheimer’s diseaseGene-silencingTauTransgenic mouse model

Identifiers

PMID27593210
PMCPMC5011353
OpenAlexW2516735412

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.