PXD068185

PXD068185 is an original dataset announced via ProteomeXchange.

Title	Muscle-specific increased expression of JAG1 improves the skeletal muscle phenotype in dystrophin-deficient mice
Description	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 (mdx5cv-JAG1) model that lacks dystrophin and overexpresses human JAG1 in striated muscles. Skeletal muscles from mdx5cv-JAG1 and mdx5cv mice were studied at 1-, 4-, and 12-mo time points. JAG1 expression in mdx5cv-JAG1 increased by 3 to 5 times compared to mdx5cv. Consequently, mdx5cv-JAG1 muscles were significantly bigger and stronger than dystrophic controls, along with an increased number of myofibers. Proteomics data show increased dysferlin in mdx5cv-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.
HostingRepository	PRIDE
AnnounceDate	2026-03-30
AnnouncementXML	Submission_2026-03-29_16:20:07.903.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-08 09:16:22	ID requested
⏵ 1	2026-03-29 16:20:08	announced

10.1073/pnas.2506437122;

de Souza Leite F, Lambert MR, Zhang TY, Conner JR, Paulo JA, Oliveira SF, Guha Thakurta S, Bowles J, Gussoni E, Gygi SP, Widrick JJ, Kunkel LM, improves the skeletal muscle phenotype in dystrophin-deficient mice. Proc Natl Acad Sci U S A, 122(39):e2506437122(2025) [pubmed]

submitter keyword: Duchenne muscular dystrophy; Jagged-1; mouse model; genetic modifier; physiology

Louis M. Kunkel
contact affiliation	Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA Department of Genetics and Pediatrics, Harvard Medical School, Boston, MA 02115, USA
contact email	kunkel@enders.tch.harvard.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/03/PXD068185

PRIDE project URI

• PRIDE
  1. PXD068185
     1. Label: PRIDE project
     2. Name: Muscle-specific increased expression of JAG1 improves the skeletal muscle phenotype in dystrophin-deficient mice