A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy
| Autor: | Nicole Wong, Diane Golebiowski, Parry Chan, Sydney Steiman, Elzbieta Hyatt, Abdalla Ahmed, Evgueni A. Ivakine, Grace J. Yang, Eleonora Maino, Tatianna Wai Ying Wong, Lindsay K, Ronald D. Cohn, Joel S. Schneider, Paul Delgado-Olguin |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology Duchenne muscular dystrophy Cardiomyopathy Medicine (miscellaneous) lcsh:Medicine medicine.disease_cause Dystrophin 0302 clinical medicine Sarcolemma Immunology and Microbiology (miscellaneous) Tachycardia Muscular dystrophy Dystroglycans Wasting Mutation biology Hypertrophic cardiomyopathy Exons Female medicine.symptom Cardiomyopathies Research Article lcsh:RB1-214 musculoskeletal diseases muscular dystrophy medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities Neuromuscular disease mouse model Neuroscience (miscellaneous) Cardiomegaly Mice Transgenic General Biochemistry Genetics and Molecular Biology deletion mutation 03 medical and health sciences medicine lcsh:Pathology Animals Muscle Strength Muscle Skeletal Base Sequence business.industry lcsh:R medicine.disease Mice Inbred C57BL Muscular Dystrophy Duchenne Disease Models Animal 030104 developmental biology biology.protein dmd CRISPR-Cas Systems business cardiomyopathy 030217 neurology & neurosurgery Gene Deletion |
| Zdroj: | Disease Models & Mechanisms, Vol 13, Iss 9 (2020) Disease Models & Mechanisms article-version (VoR) Version of Record |
| ISSN: | 1754-8411 1754-8403 |
| Popis: | Duchenne muscular dystrophy (DMD) is a life-threatening neuromuscular disease caused by the lack of dystrophin, resulting in progressive muscle wasting and locomotor dysfunctions. By adulthood, almost all patients also develop cardiomyopathy, which is the primary cause of death in DMD. Although there has been extensive effort in creating animal models to study treatment strategies for DMD, most fail to recapitulate the complete skeletal and cardiac disease manifestations that are presented in affected patients. Here, we generated a mouse model mirroring a patient deletion mutation of exons 52-54 (Dmd Δ52-54). The Dmd Δ52-54 mutation led to the absence of dystrophin, resulting in progressive muscle deterioration with weakened muscle strength. Moreover, Dmd Δ52-54 mice present with early-onset hypertrophic cardiomyopathy, which is absent in current pre-clinical dystrophin-deficient mouse models. Therefore, Dmd Δ52-54 presents itself as an excellent pre-clinical model to evaluate the impact on skeletal and cardiac muscles for both mutation-dependent and -independent approaches. Summary: The Dmd Δ52-54 mouse model, which carries a deletion of Dmd exons 52-54, emulates Duchenne muscular dystrophy disease progression in skeletal muscle and has early onset of cardiac functional abnormalities. |
| Databáze: | OpenAIRE |
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