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Authors
Vieira, Natassia M.Elvers, Ingegerd
Alexander, Matthew S.
Moreira, Yuri B.
Eran, Alal
Gomes, Juliana P.
Marshall, Jamie L.
Karlsson, Elinor K.
Verjovski-Almeida, Sergio
Lindblad-Toh, Kerstin
Kunkel, Louis M.
Zatz, Mayana
UMass Chan Affiliations
Program in Bioinformatics and Integrative BiologyDocument Type
Journal ArticlePublication Date
2015-11-19Keywords
DMDJagged1
dystrophin
genetic modifier
muscle
Bioinformatics
Computational Biology
Genetics
Genomics
Molecular Genetics
Musculoskeletal Diseases
Metadata
Show full item recordAbstract
Duchenne muscular dystrophy (DMD), caused by mutations at the dystrophin gene, is the most common form of muscular dystrophy. There is no cure for DMD and current therapeutic approaches to restore dystrophin expression are only partially effective. The absence of dystrophin in muscle results in dysregulation of signaling pathways, which could be targets for disease therapy and drug discovery. Previously, we identified two exceptional Golden Retriever muscular dystrophy (GRMD) dogs that are mildly affected, have functional muscle, and normal lifespan despite the complete absence of dystrophin. Now, our data on linkage, whole-genome sequencing, and transcriptome analyses of these dogs compared to severely affected GRMD and control animals reveals that increased expression of Jagged1 gene, a known regulator of the Notch signaling pathway, is a hallmark of the mild phenotype. Functional analyses demonstrate that Jagged1 overexpression ameliorates the dystrophic phenotype, suggesting that Jagged1 may represent a target for DMD therapy in a dystrophin-independent manner.Source
Cell. 2015 Nov 19;163(5):1204-13. doi: 10.1016/j.cell.2015.10.049. Epub 2015 Nov 12. Link to article on publisher's siteDOI
10.1016/j.cell.2015.10.049Permanent Link to this Item
http://hdl.handle.net/20.500.14038/25929PubMed ID
26582133Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.cell.2015.10.049