Evidence map›Paper›PMID 25168898›Full record

ArticleInvestigative ophthalmology & visual science2014

Expression of the HSF4 DNA binding domain-EGFP hybrid gene recreates early childhood lamellar cataract in transgenic mice.

Rajendra K Gangalum, Zhe Jing, Ankur M Bhat, Josh Lee, Yoshiko Nagaoka, Sophie X Deng, Meisheng Jiang, Suraj P Bhat

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

Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 41% 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

4 citing papers in PubMed, 6 citations in OpenAlex.

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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

8 authors at 2 institutions in 1 country.

Rajendra K GangalumJules Stein Eye Institute, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States.
Zhe JingJules Stein Eye Institute, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States.
Ankur M BhatJules Stein Eye Institute, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States.
Josh LeeJules Stein Eye Institute, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States Department of Molecular and Medical Pharmacology, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States Molecular Biology Institute and Brain Research Institute, University of California Los Angeles, Los Angeles, California, United States.
Yoshiko NagaokaDepartment of Molecular and Medical Pharmacology, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States.
Sophie X DengMolecular Biology Institute and Brain Research Institute, University of California Los Angeles, Los Angeles, California, United States.
Meisheng JiangDepartment of Molecular and Medical Pharmacology, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States.
Suraj P BhatJules Stein Eye Institute, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California, United States Molecular Biology Institute and Brain Research Institute, University of California Los Angeles, Los Angeles, California, United States.
University of California, Los Angeles · USDoheny Eye Institute · US

Funding

GENE EXPRESSION IN THE NORMAL AND CATARACTOUS LENSR01EY006044 · NEI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BHAT, SURAJ P · 1985 to 2010
$4.4M
NEI NIH HHS R01 EY006044
6 · The paper itself

Abstract

purposeThe clinical management of cataracts in infancy involves surgical removal of the lens to ensure transmission of light to the retina, which is essential for normal neural development of the infant. This surgery, however, entails a lifelong follow-up and impaired vision. To our knowledge, no animal models recapitulate human lamellar opacities, the most prevalent form of early childhood cataracts. We present data on the recreation of the human lamellar cataract phenotype in transgenic mice.

methodsMutations in the DNA binding domain (DBD) of the heat shock transcription factor 4 (HSF4) are known to be associated with early childhood autosomal dominant lamellar cataract. We used bacterial artificial chromosome (BAC) transgenesis to express a hybrid gene: Hsf4 (DBD)-enhanced green fluorescent protein (EGFP), by recombineering EGFP sequences into the DBD of the Hsf4 gene, to interfere with the DNA binding properties of Hsf4.

resultsWe recapitulated the human lamellar cataract, in its temporal as well as spatial presentation, within the transgenic mouse lens. This phenotype was reproduced faithfully using four different BACs, indicating that EGFP can be used to target transcription factor function in transgenic mice. Molecular and cell biological examination of early postnatal transgenic lens reveals impairment of secondary fiber cell differentiation.

conclusionsRecreation of the human lamellar cataract phenotype in mice allows investigation of this human pathology at a level not possible previously and points to the relevance of fiber cell heterogeneity dictated by fiber cell-specific gene activity in the biogenesis of the lamellar cataract.

Indexed as

Gene Expression Regulation, DevelopmentalAnimalsCataractCells, CulturedChildDisease Models, AnimalDNADNA-Binding ProteinsGenes, erbB-1GenotypeHeat Shock Transcription FactorsHumansImmunoblottingMiceMice, TransgenicReal-Time Polymerase Chain ReactionDNADNA-Binding ProteinsHeat Shock Transcription FactorsHsf4 protein, mouseTranscription FactorsBACscataractHSF4lenstransgenic mice

Identifiers

PMID25168898
PMCPMC4231995
OpenAlexW1980693706

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.