Evidence map›Paper›PMID 29178881›Full record

ArticleJournal of biomedical science2017

Atrial ERK1/2 activation in the embryo leads to incomplete Septal closure: a novel mouse model of atrial Septal defect.

Che-Chung Yeh, Yanying Fan, Yi-Lin Yang, Michael J Mann

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

Article in Journal of biomedical science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.1field-weighted citation impact, top 48% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Guidelines for in vivo models of developmental programming of cardiovascular disease risk.American journal of physiology. Heart and circulatory physiology · 2024
    Review
  2. 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

4 authors at 1 institution in 1 country.

Che-Chung YehCardiothoracic Translational Research Laboratory, University of California, San Francisco, San Francisco, CA, USA.
Yanying FanCardiothoracic Translational Research Laboratory, University of California, San Francisco, San Francisco, CA, USA.
Yi-Lin YangCardiothoracic Translational Research Laboratory, University of California, San Francisco, San Francisco, CA, USA.
Michael J MannCardiothoracic Translational Research Laboratory, University of California, San Francisco, San Francisco, CA, USA. Michael.Mann@ucsf.edu.
University of California, San Francisco · US

Funding

ERK Signaling and a Hybrid Surgical/Molecular Approach for Chronic Heart FailureR01HL083118 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MANN, MICHAEL J · 2006 to 2016
$4.2M
The role of S1P signaling in surgical cardiac remodelingK08HL079239 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MANN, MICHAEL J · 2006 to 2010
$609k
National Heart, Lung, and Blood Institute K08HL079239National Heart, Lung, and Blood Institute R01HL083118NHLBI NIH HHS K08 HL079239NHLBI NIH HHS R01 HL083118
6 · The paper itself

Abstract

backgroundMEK1 mutation and activated MAPK signaling has been found in patients with RASopathies and abnormal cardiac development. Previous studies have suggested that regulation of fetal MAPK signaling is essential for normal cardiac development. We investigated the effect of active MEK1 overexpression on fetal atrial septal development. METHODS AND

resultsAn inducible double transgenic (DTg) mouse model was developed in which cardiac-specific fetal expression of a constitutively active form of human MEK1 (aMEK1) was induced primarily in the atrium via the withdrawal of doxycycline from the drinking water of pregnant mice. Atrial septal defect (ASD) was found in 51% (23/45) of DTg mice. Fifty-two percent (12/23) of ASD mice died before weaning, and surviving ASD mice exhibited hypertrophic hearts with enlarged right atria and decreased fractional shorting (40 ± 2% vs. 48 ± 0%, p < 0.05). The model mimicked human ASD in several key clinical features: severe ASD was associated with growth impairment; ASD-specific mortality was highest within the early postnatal period; despite an even distribution of ASD among the sexes, early mortality was significantly higher in males. The expression of aMEK1 and increased phosphorylation of ERK1/2 was documented via Western blot in DTg fetal hearts, with the largest increases seen in atrial tissue. In an alternative transgenic aMEK1 model with elevated atrial MKP3 expression and corresponding suppression of increases in ERK1/2 phosphorylation, animals did not develop ASD.

conclusionThis new model of ASD suggests that enhanced atrial MEK1-ERK1/2 signaling during fetal development disrupts normal atrial septation, possibly regulated by the balance of ERK1/2 phosphorylation.

Indexed as

AnimalsDisease Models, AnimalFemaleHeart AtriaHeart Septal Defects, AtrialHumansMaleMAP Kinase Kinase 1MAP Kinase Signaling SystemMiceMice, TransgenicMap2k1 protein, mouseMAP Kinase Kinase 1Atrial septal defectMAP kinase phosphataseMitogen-activated protein kinaseMitogen-activated protein kinase pathwayRASopathies

Identifiers

PMID29178881
PMCPMC5702213
OpenAlexW2768370678

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.