Evidence mapPaperPMID 40490752Full record

ArticleSkeletal muscle2025

Extensive striated muscle damage in a rat model of Duchenne muscular dystrophy with Dmd exons 10-17 duplication.

Jean-Daniel Masson, Valentina Taglietti, François Ruby, Hiroya Ono, Nadir Mouri, Alan Jorge, Laurent Guillaud, Laurent Tiret, Frederic Relaix

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Article in Skeletal muscle, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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field-weighted citation impact
1 · What the graph read from it

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Jean-Daniel Masson *Univ Paris-Est Créteil, INSERM, U955 IMRB, Créteil, F-94010, France.ORCID 0000-0001-6861-9967
Valentina Taglietti *Univ Paris-Est Créteil, INSERM, U955 IMRB, Créteil, F-94010, France.ORCID 0000-0001-8639-8088
François RubyUniv Paris-Est Créteil, INSERM, U955 IMRB, Créteil, F-94010, France.
Hiroya OnoUniv Paris-Est Créteil, INSERM, U955 IMRB, Créteil, F-94010, France.ORCID 0000-0002-8439-5657
Nadir MouriDépartement de Biochimie-Pharmacologie, AP-HP, Hôpitaux Universitaires Henri Mondor, Créteil, F-94010, France.
Alan JorgeUniv Paris-Est Créteil, INSERM, U955 IMRB, Créteil, F-94010, France.
Laurent GuillaudUniv Paris-Est Créteil, INSERM, U955 IMRB, Créteil, F-94010, France.
Laurent Tiret *Univ Paris-Est Créteil, INSERM, U955 IMRB, Créteil, F-94010, France.ORCID 0000-0001-8573-8335
Frederic Relaix *Univ Paris-Est Créteil, INSERM, U955 IMRB, Créteil, F-94010, France. frederic.relaix@inserm.fr.ORCID 0000-0003-1270-1472

Funding

AFM-Téléthon 19507, 22946European MAGIC Project consortium 101080690Fondation pour la Recherche Médicale EQU20200301021
6 · The paper itself

Abstract

backgroundDuchenne muscular dystrophy (DMD) mainly affects young boys with out-of-frame mutations in the DMD gene, leading to dystrophin deficiency. This loss disrupts the assembly of the sarcolemmal dystrophin-associated glycoprotein complex, resulting in membrane fragility and damage during muscle contraction-relaxation cycles. Consequently, patients experience progressive muscle weakness, loss of ambulation and cardiorespiratory failure. Gene therapy represents one of the most promising therapeutic approaches, requiring rigorous preclinical validation of candidate strategies. While several preclinical models of dystrophin deficiency mimic point mutations or exon deletions, no existing rat model accurately replicates DMD gene duplications, which account for approximately 10% of DMD cases.

methodsUsing CRISPR/Cas9 genome editing, we generated a ~ 125 kbp duplication encompassing exons 10-17 of the Dmd gene in Sprague Dawley rats. To characterise disease progression in these rats, we assessed biochemical, histological and functional biomarkers at 6 and 10 months of age, comparing them to their healthy littermates.

resultsWe established the R-DMDdup10-17 line. The microstructure of limb, diaphragm and cardiac muscles of R-DMDdup10-17 (DMD) rats exhibited dystrophic changes at 6 and 10 months, including loss of myofibres and fibrosis. These alterations led to a significant body mass reduction, muscle weakness (including diaphragm deficiency) and cardiac electrical defects. Premature lethality was observed between 10 and 13 months.

conclusionDuplication of the Dmd genomic region encompassing exons 10 to 17 in rats results in dystrophin deficiency, severe striated muscle dystrophy, and premature death. The R-DMDdup10-17 line represents the first reported genetic model of a severe and early lethal duplication variant in the Dmd gene. It provides a critical tool for assessing targeted gene therapies aimed to correct such mutations.

Indexed as

DystrophinGene DuplicationMuscle, StriatedMuscular Dystrophy, DuchenneAnimalsCRISPR-Cas SystemsDisease Models, AnimalExonsGene EditingMaleRatsRats, Sprague-DawleyDystrophinCongenital myopathyECGhs-cTnTInter-individual data correctionMYOM3MyonecrosisNeuromuscular disorderNotched T wavePlethysmography

Identifiers

PMID40490752
PMCPMC12147255

What Socratic holds

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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 Socratic graph.