Jagged 1 Rescues the Duchenne Muscular Dystrophy Phenotype
Autor: | Yuri B Moreira, J. Gomes, Kerstin Lindblad-Toh, Natássia M. Vieira, Matthew S. Alexander, Elinor K. Karlsson, Ingegerd Elvers, Sergio Verjovski-Almeida, Alal Eran, Jamie L. Marshall, Mayana Zatz, Louis M. Kunkel |
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Rok vydání: | 2015 |
Předmět: |
Male
muscle Duchenne muscular dystrophy Penetrance Dystrophin Mice 0302 clinical medicine Serrate-Jagged Proteins Dog Diseases Muscular dystrophy Zebrafish genetic modifier 0303 health sciences musculoskeletal system Phenotype Pedigree Intercellular Signaling Peptides and Proteins Female ITGA7 musculoskeletal diseases congenital hereditary and neonatal diseases and abnormalities Notch signaling pathway Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Dogs DMD Utrophin medicine Animals 030304 developmental biology Cell Proliferation Biochemistry Genetics and Molecular Biology(all) Calcium-Binding Proteins Membrane Proteins Muscular Dystrophy Animal Zebrafish Proteins medicine.disease biology.organism_classification GENÉTICA MÉDICA Muscular Dystrophy Duchenne Disease Models Animal Jagged1 Cancer research biology.protein Transcriptome 030217 neurology & neurosurgery Jagged-1 Protein Genome-Wide Association Study |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
ISSN: | 1097-4172 |
Popis: | SummaryDuchenne 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.PaperClip |
Databáze: | OpenAIRE |
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