Identification of candidate miRNA biomarkers for facioscapulohumeral muscular dystrophy using DUX4-based mouse models
| Autor: | Takako I. Jones, Andreia M Nunes, M. O. Ramírez, Peter L. Jones |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
Genetically modified mouse Neuromuscular Disease Models congenital hereditary and neonatal diseases and abnormalities Neuroscience (miscellaneous) Medicine (miscellaneous) Biology Skeletal Myocytes Bioinformatics General Biochemistry Genetics and Molecular Biology fshd Mice Immunology and Microbiology (miscellaneous) DUX4 microRNA dux4 Pathology medicine Animals Humans RB1-214 Facioscapulohumeral muscular dystrophy Muscle Skeletal Homeodomain Proteins Skeletal muscle medicine.disease Phenotype Muscular Dystrophy Facioscapulohumeral nervous system diseases MicroRNAs medicine.anatomical_structure biomarker Medicine Biomarker (medicine) mir-206 Biomarkers Research Article mirna |
| Zdroj: | Disease Models & Mechanisms, Vol 14, Iss 8 (2021) Disease Models & Mechanisms article-version (VoR) Version of Record |
| ISSN: | 1754-8411 1754-8403 |
| DOI: | 10.1242/dmm.049016 |
| Popis: | Facioscapulohumeral muscular dystrophy (FSHD) is caused by misexpression of DUX4 in skeletal myocytes. As DUX4 is the key therapeutic target in FSHD, surrogate biomarkers of DUX4 expression in skeletal muscle are critically needed for clinical trials. Although no natural animal models of FSHD exist, transgenic mice with inducible DUX4 expression in skeletal muscles rapidly develop myopathic phenotypes consistent with FSHD. Here, we established a new, more-accurate FSHD-like mouse model based on chronic DUX4 expression in a small fraction of skeletal myonuclei that develops pathology mimicking key aspects of FSHD across its lifespan. Utilizing this new aged mouse model and DUX4-inducible mouse models, we characterized the DUX4-related microRNA signatures in skeletal muscles, which represent potential biomarkers for FSHD. We found increased expression of miR-31-5p and miR-206 in muscles expressing different levels of DUX4 and displaying varying degrees of pathology. Importantly, miR-206 expression is significantly increased in serum samples from FSHD patients compared with healthy controls. Our data support miR-31-5p and miR-206 as new potential regulators of muscle pathology and miR-206 as a potential circulating biomarker for FSHD. This article has an associated First Person interview with the first author of the paper. Summary: Candidate miRNA biomarkers for facioscapulohumeral muscular dystrophy (FSHD) were identified using FSHD-like mouse models that present cumulative pathology from chronic expression of DUX4 in skeletal muscles and confirmed in FSHD patient serum. |
| Databáze: | OpenAIRE |
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