Evidence map›Paper›PMID 24829265›Full record

ArticleCirculation research2014

β-Myosin heavy chain variant Val606Met causes very mild hypertrophic cardiomyopathy in mice, but exacerbates HCM phenotypes in mice carrying other HCM mutations.

Robert Blankenburg, Katarzyna Hackert, Sebastian Wurster, René Deenen, J G Seidman, Christine E Seidman, Martin J Lohse, Joachim P Schmitt

Open access · bronzeAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

24 citing papers in PubMed, 50 citations in OpenAlex.

  1. The R120G knock-in mutation in αB-crystallin is insufficient to induce cardiomyopathy in mice.American journal of physiology. Heart and circulatory physiology · 2026
    Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. MYH7 in cardiomyopathy and skeletal muscle myopathy.Molecular and cellular biochemistry · 2024
    Review
  7. Article
  8. Article
  9. Article
  10. Genetic Testing in Patients with Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2021
    Review
  11. Article
  12. Article
  13. Identifying modifier genes for hypertrophic cardiomyopathy.Journal of molecular and cellular cardiology · 2020
    Article
  14. Article
  15. Article
  16. Article
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  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Robert BlankenburgFrom the Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany (R.B., S.W., M.J.L., J.P.S.); Institute of Pharmacology and Clinical Pharmacology, University Hospital Düsseldorf and Cardiovascular Research Institute Düsseldorf (CARID), Heinrich-Heine-University, Düsseldorf, Germany (K.H., J.P.S.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (C.E.S.); Department of Genetics, Harvard Medical School, Boston, MA (J.G.S.); and Bio-Medical Research Center (BMFZ), Heinrich-Heine-University, Düsseldorf, Germany (R.D.).
Katarzyna HackertFrom the Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany (R.B., S.W., M.J.L., J.P.S.); Institute of Pharmacology and Clinical Pharmacology, University Hospital Düsseldorf and Cardiovascular Research Institute Düsseldorf (CARID), Heinrich-Heine-University, Düsseldorf, Germany (K.H., J.P.S.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (C.E.S.); Department of Genetics, Harvard Medical School, Boston, MA (J.G.S.); and Bio-Medical Research Center (BMFZ), Heinrich-Heine-University, Düsseldorf, Germany (R.D.).
Sebastian WursterFrom the Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany (R.B., S.W., M.J.L., J.P.S.); Institute of Pharmacology and Clinical Pharmacology, University Hospital Düsseldorf and Cardiovascular Research Institute Düsseldorf (CARID), Heinrich-Heine-University, Düsseldorf, Germany (K.H., J.P.S.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (C.E.S.); Department of Genetics, Harvard Medical School, Boston, MA (J.G.S.); and Bio-Medical Research Center (BMFZ), Heinrich-Heine-University, Düsseldorf, Germany (R.D.).
René DeenenFrom the Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany (R.B., S.W., M.J.L., J.P.S.); Institute of Pharmacology and Clinical Pharmacology, University Hospital Düsseldorf and Cardiovascular Research Institute Düsseldorf (CARID), Heinrich-Heine-University, Düsseldorf, Germany (K.H., J.P.S.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (C.E.S.); Department of Genetics, Harvard Medical School, Boston, MA (J.G.S.); and Bio-Medical Research Center (BMFZ), Heinrich-Heine-University, Düsseldorf, Germany (R.D.).
J G SeidmanFrom the Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany (R.B., S.W., M.J.L., J.P.S.); Institute of Pharmacology and Clinical Pharmacology, University Hospital Düsseldorf and Cardiovascular Research Institute Düsseldorf (CARID), Heinrich-Heine-University, Düsseldorf, Germany (K.H., J.P.S.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (C.E.S.); Department of Genetics, Harvard Medical School, Boston, MA (J.G.S.); and Bio-Medical Research Center (BMFZ), Heinrich-Heine-University, Düsseldorf, Germany (R.D.).
Christine E SeidmanFrom the Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany (R.B., S.W., M.J.L., J.P.S.); Institute of Pharmacology and Clinical Pharmacology, University Hospital Düsseldorf and Cardiovascular Research Institute Düsseldorf (CARID), Heinrich-Heine-University, Düsseldorf, Germany (K.H., J.P.S.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (C.E.S.); Department of Genetics, Harvard Medical School, Boston, MA (J.G.S.); and Bio-Medical Research Center (BMFZ), Heinrich-Heine-University, Düsseldorf, Germany (R.D.).
Martin J LohseFrom the Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany (R.B., S.W., M.J.L., J.P.S.); Institute of Pharmacology and Clinical Pharmacology, University Hospital Düsseldorf and Cardiovascular Research Institute Düsseldorf (CARID), Heinrich-Heine-University, Düsseldorf, Germany (K.H., J.P.S.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (C.E.S.); Department of Genetics, Harvard Medical School, Boston, MA (J.G.S.); and Bio-Medical Research Center (BMFZ), Heinrich-Heine-University, Düsseldorf, Germany (R.D.).
Joachim P SchmittFrom the Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany (R.B., S.W., M.J.L., J.P.S.); Institute of Pharmacology and Clinical Pharmacology, University Hospital Düsseldorf and Cardiovascular Research Institute Düsseldorf (CARID), Heinrich-Heine-University, Düsseldorf, Germany (K.H., J.P.S.); Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (C.E.S.); Department of Genetics, Harvard Medical School, Boston, MA (J.G.S.); and Bio-Medical Research Center (BMFZ), Heinrich-Heine-University, Düsseldorf, Germany (R.D.). joachim.schmitt@uni-duesseldorf.de.
Brigham and Women's Hospital · US

Funding

Defining Pathways from Gene Mutation to Heart FailureR01HL080494 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI CHEN, CHRISTOPHER S, SEIDMAN, CHRISTINE E · 2005 to 2024
$9.4M
Molecular Signaling in Hypertrophic CardiomyopathyR01HL084553 · NHLBI · HARVARD MEDICAL SCHOOL · PI SEIDMAN, JONATHAN G · 2007 to 2022
$5.9M
Molecular Biology of Cardiac DiseaseR13HL076493 · NHLBI · KEYSTONE SYMPOSIA · PI SEIDMAN, JONATHAN G · 2004 to 2004
$10k
NHLBI NIH HHS R01 HL080494NHLBI NIH HHS R01 HL084553NHLBI NIH HHS R13 HL076493
6 · The paper itself

Abstract

rationaleApproximately 40% of hypertrophic cardiomyopathy (HCM) is caused by heterozygous missense mutations in β-cardiac myosin heavy chain (β-MHC). Associating disease phenotype with mutation is confounded by extensive background genetic and lifestyle/environmental differences between subjects even from the same family.

objectiveTo characterize disease caused by β-cardiac myosin heavy chain Val606Met substitution (VM) that has been identified in several HCM families with wide variation of clinical outcomes, in mice. METHODS AND

resultsUnlike 2 mouse lines bearing the malignant myosin mutations Arg453Cys (RC/+) or Arg719Trp (RW/+), VM/+ mice with an identical inbred genetic background lacked hallmarks of HCM such as left ventricular hypertrophy, disarray of myofibers, and interstitial fibrosis. Even homozygous VM/VM mice were indistinguishable from wild-type animals, whereas RC/RC- and RW/RW-mutant mice died within 9 days after birth. However, hypertrophic effects of the VM mutation were observed both in mice treated with cyclosporine, a known stimulator of the HCM response, and compound VM/RC heterozygous mice, which developed a severe HCM phenotype. In contrast to all heterozygous mutants, both systolic and diastolic function of VM/RC hearts was severely impaired already before the onset of cardiac remodeling.

conclusionsThe VM mutation per se causes mild HCM-related phenotypes; however, in combination with other HCM activators it exacerbates the HCM phenotype. Double-mutant mice are suitable for assessing the severity of benign mutations.

Indexed as

Amino Acid SubstitutionMutation, MissensePoint MutationAnimalsCardiac MyosinsCardiomyopathy, Hypertrophic, FamilialCyclosporineDisease Models, AnimalGene Knock-In TechniquesGenotypeHumansHypertrophy, Left VentricularMiceModels, MolecularMyocardial ContractionMyosin Heavy ChainsCardiac MyosinsCyclosporineMyh6 protein, mouseMYH7 protein, humanMyosin Heavy ChainsVentricular Myosinscardiomyopathiesgeneticshypertrophymyocardial contractionmyosins

Identifiers

PMID24829265
PMCPMC4086907
OpenAlexW2524168389

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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.