Evidence map›Paper›PMID 26271004›Full record

ArticleGenesis (New York, N.Y. : 2000)2015

BAC transgenic zebrafish reveal hypothalamic enhancer activity around obesity associated SNP rs9939609 within the human FTO gene.

Silke Rinkwitz, Fan-Suo Geng, Elizabeth Manning, Maximiliano Suster, Koichi Kawakami, Thomas S Becker

Open access · bronzeAbstract read
In one paragraph

Article in Genesis (New York, N.Y. : 2000), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact, top 96% 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

5 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Technologies, strategies, and cautions when deconvoluting genome-wide association signals: FTO in focus.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2023
    Review
  3. Review
  4. Review
  5. Article
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

6 authors at 3 institutions in 3 countries.

Silke RinkwitzBrain and Mind Research Institute, School of Medicine, University of Sydney, Camperdown, New South Wales, Australia.
Fan-Suo GengBrain and Mind Research Institute, School of Medicine, University of Sydney, Camperdown, New South Wales, Australia.
Elizabeth ManningBrain and Mind Research Institute, School of Medicine, University of Sydney, Camperdown, New South Wales, Australia.
Maximiliano SusterNeural Circuits and Behavior Group, Uni Research AS, Bergen, Norway.
Koichi KawakamiDivision of Molecular and Developmental Biology, National Institute of Genetics, Mishima, Shizuoka, Japan.
Thomas S BeckerBrain and Mind Research Institute, School of Medicine, University of Sydney, Camperdown, New South Wales, Australia.
University of Sydney · AUNational Institute of Genetics · JPUni Research (Norway) · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Single Nucleotide Polymorphisms in FTO intron 1 have been associated with obesity risk, leading to the hypothesis that FTO is the obesity-related gene. However, other studies have shown that the FTO gene is part of the regulatory domain of the neighboring IRX3 gene and that enhancers in FTO intron 1 regulate IRX3. While Irx3 activity was shown to be necessary in the hypothalamus for the metabolic function of Irx3 in mouse, no enhancers with hypothalamic activity have been demonstrated in the risk-associated region within FTO. In order to identify potential enhancers at the human FTO locus in vivo, we tested regulatory activity in FTO intron 1 using BAC transgenesis in zebrafish. A minimal gata2 promoter-GFP cassette was inserted 1.3 kb upstream of the obesity associated SNP rs9939609 in a human FTO BAC plasmid. In addition to the previously identified expression domains in notochord and kidney, human FTO BAC:GFP transgenic zebrafish larvae expressed GFP in the ventral posterior tuberculum, the posterior hypothalamus and the anterior brainstem, which are also expression domains of zebrafish irx3a. In contrast, an in-frame insertion of a GFP cassette at the FTO start codon resulted in weak ubiquitous GFP expression indicating that the promoter of FTO does likely not react to enhancers located in the obesity risk-associated region.

Indexed as

Polymorphism, Single NucleotideAlpha-Ketoglutarate-Dependent Dioxygenase FTOAnimalsAnimals, Genetically ModifiedBrainGene Expression Regulation, DevelopmentalGenetic Predisposition to DiseaseGreen Fluorescent ProteinsHomeodomain ProteinsHumansHypothalamusImmunohistochemistryIn Situ HybridizationIntronsLarvaMicroscopy, ConfocalAlpha-Ketoglutarate-Dependent Dioxygenase FTOFTO protein, humanGreen Fluorescent ProteinsHomeodomain ProteinsProteinsTranscription FactorsZebrafish ProteinsgeneticsgenomicsGWASmammalorganismtissue

Identifiers

PMID26271004
PMCPMC5054831
OpenAlexW1955085225

What OpenQuestion holds

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LicenceCC BY-NC
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.