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Record W4414435897 · doi:10.1073/pnas.2506437122

Muscle-specific increased expression of <i>JAG1</i> improves the skeletal muscle phenotype in dystrophin-deficient mice

2025· article· en· W4414435897 on OpenAlexfundno aff
Felipe de Souza Leite, Matthias Lambert, Tracy Zhang, James R. Conner, João A. Paulo, Sheldon Furtado Oliveira, Sanjukta Guha Thakurta, Jennifer Bowles, Emanuela Gussoni, Steven P. Gygi, Jeffrey J. Widrick, Louis M. Kunkel

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMuscle Physiology and Disorders
Canadian institutionsnot available
FundersBernard F. and Alva B. Gimbel FoundationNational Institute of Arthritis and Musculoskeletal and Skin DiseasesIntellectual and Developmental Disabilities Research CenterNational Cancer InstituteNational Institutes of HealthConselho Nacional de Desenvolvimento Científico e TecnológicoDefeat Duchenne CanadaMuscular Dystrophy AssociationFrench Muscular Dystrophy AssociationAmerican Heart Association
KeywordsDysferlinMuscular dystrophySkeletal muscleDystrophinDuchenne muscular dystrophyPhenotypeITGA7Genetically modified mouseTransgene

Abstract

fetched live from OpenAlex

Therapeutic strategies for Duchenne muscular dystrophy (DMD) will likely require complementary approaches. One possibility is to explore genetic modifiers that improve muscle regeneration and function. The beneficial effects of the overexpression of Jagged-1 were described in escaper golden retriever muscular dystrophy (GRMD) dogs that had a near-normal life and validated in dystrophin-deficient zebrafish. To clarify the underlying biology of JAG1 overexpression in dystrophic muscles, we generated a transgenic mouse (mdx 5cv - JAG1 ) model that lacks dystrophin and overexpresses human JAG1 in striated muscles. Skeletal muscles from mdx 5cv - JAG1 and mdx 5cv mice were studied at 1-, 4-, and 12-mo time points. JAG1 expression in mdx 5cv - JAG1 increased by 3 to 5 times compared to mdx 5cv . Consequently, mdx 5cv - JAG1 muscles were significantly bigger and stronger than dystrophic controls, along with an increased number of myofibers. Proteomics data show increased dysferlin in mdx 5cv - JAG1 muscles and an association of the histone methyltransferase Nsd1 with the phenotype. Our data support the positive effect of JAG1 overexpression in dystrophic muscles.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.265
Teacher spread0.252 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

Explore more

Same venueProceedings of the National Academy of Sciences→Same topicMuscle Physiology and Disorders→French-language works237,207→