Evidence map›Paper›PMID 30281092›Full record

ArticleHuman molecular genetics2019

Cmah-dystrophin deficient mdx mice display an accelerated cardiac phenotype that is improved following peptide-PMO exon skipping treatment.

Corinne A Betts, Graham McClorey, Richard Healicon, Suzan M Hammond, Raquel Manzano, Sofia Muses, Vicky Ball, Caroline Godfrey, Thomas M Merritt, Tirsa van Westering and 6 more

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

Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

9 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Cardiac CIP protein regulates dystrophic cardiomyopathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Article
  5. The multifaceted view of heart problem in Duchenne muscular dystrophy.Cellular and molecular life sciences : CMLS · 2021
    Review
  6. Review
  7. Mouse models for muscular dystrophies: an overview.Disease models & mechanisms · 2020
    Review
  8. Review
  9. Review
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

16 authors at 5 institutions in 1 country.

Corinne A BettsDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK.
Graham McCloreyDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK.
Richard HealiconDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK.
Suzan M HammondDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK.
Raquel ManzanoDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK.
Sofia MusesDepartment of Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London, UK.
Vicky BallDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK.
Caroline GodfreyDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK.
Thomas M MerrittClinical Biomanufacturing Facility, Nuffield Department of Clinical Medicine, University of Oxford, Old Road, Oxford, UK.
Tirsa van WesteringDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK.
Liz O'DonovanMedical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK.
Kim E WellsDepartment of Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London, UK.
Michael J GaitMedical Research Council, Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, UK.
Dominic J WellsDepartment of Comparative Biomedical Sciences, Royal Veterinary College, Royal College Street, London, UK.
Damian TylerDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK.
Matthew J WoodDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK.
University of Oxford · GBRoyal Veterinary College · GBScience Oxford · GBMedical Research Council · GBMRC Laboratory of Molecular Biology · GB

Funding

British Heart Foundation FS/10/002/28078British Heart Foundation FS/14/17/30634British Heart Foundation FS/19/18/34252British Heart Foundation PG/14/2/30595British Heart Foundation RG/11/9/28921Medical Research Council G0601490Medical Research Council G0900887Medical Research Council MC_U105178803Medical Research Council MR/L013142/1Medical Research Council MR/N024850/1Medical Research Council MR/R025312/1
6 · The paper itself

Abstract

Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin protein, leading to progressive muscle weakness and premature death due to respiratory and/or cardiac complications. Cardiac involvement is characterized by progressive dilated cardiomyopathy, decreased fractional shortening and metabolic dysfunction involving reduced metabolism of fatty acids-the major cardiac metabolic substrate. Several mouse models have been developed to study molecular and pathological consequences of dystrophin deficiency, but do not recapitulate all aspects of human disease pathology and exhibit a mild cardiac phenotype. Here we demonstrate that Cmah (cytidine monophosphate-sialic acid hydroxylase)-deficient mdx mice (Cmah-/-;mdx) have an accelerated cardiac phenotype compared to the established mdx model. Cmah-/-;mdx mice display earlier functional deterioration, specifically a reduction in right ventricle (RV) ejection fraction and stroke volume (SV) at 12 weeks of age and decreased left ventricle diastolic volume with subsequent reduced SV compared to mdx mice by 24 weeks. They further show earlier elevation of cardiac damage markers for fibrosis (Ctgf), oxidative damage (Nox4) and haemodynamic load (Nppa). Cardiac metabolic substrate requirement was assessed using hyperpolarized magnetic resonance spectroscopy indicating increased in vivo glycolytic flux in Cmah-/-;mdx mice. Early upregulation of mitochondrial genes (Ucp3 and Cpt1) and downregulation of key glycolytic genes (Pdk1, Pdk4, Ppara), also denote disturbed cardiac metabolism and shift towards glucose utilization in Cmah-/-;mdx mice. Moreover, we show long-term treatment with peptide-conjugated exon skipping antisense oligonucleotides (20-week regimen), resulted in 20% cardiac dystrophin protein restoration and significantly improved RV cardiac function. Therefore, Cmah-/-;mdx mice represent an appropriate model for evaluating cardiac benefit of novel DMD therapeutics.

Indexed as

AnimalsCardiomyopathy, DilatedCarnitine O-PalmitoyltransferaseConnective Tissue Growth FactorCytidine MonophosphateDisease Models, AnimalDystrophinExonsGenetic TherapyHeartMaleMiceMice, Inbred mdxMixed Function OxygenasesMorpholinosMuscular Dystrophy, DuchenneCarnitine O-PalmitoyltransferaseCCN2 protein, mouseConnective Tissue Growth FactorCPT1B protein, mouseCytidine MonophosphateDystrophinMixed Function OxygenasesMorpholinosNADPH Oxidase 4Nox4 protein, mouseOligonucleotides, AntisensePeptidesUcp3 protein, mouseUncoupling Protein 3

Identifiers

PMID30281092
PMCPMC6337703
OpenAlexW2895413882

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.