Pathological evaluation of rats carrying in-frame mutations in the dystrophin gene: a new model of Becker muscular dystrophy
| Autor: | Takashi Matsuwaki, Keitaro Yamanouchi, Masao Daimon, Masugi Nishihara, Tetsuya Nagata, Hidetoshi Sugihara, Tomoko Okano, Takanori Shiga, Koichi Kimura, Naomi Teramoto, Masafumi Matsuo, Taku Shirakawa, Katsuyuki Nakamura |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
musculoskeletal diseases
medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities Duchenne muscular dystrophy Rat model Neuroscience (miscellaneous) Medicine (miscellaneous) lcsh:Medicine General Biochemistry Genetics and Molecular Biology dystrophin Open Reading Frames Sarcolemma Immunology and Microbiology (miscellaneous) Internal medicine medicine lcsh:Pathology Animals Protein Isoforms Muscular dystrophy Dystroglycans Muscle Skeletal Pathological X chromosome biology Base Sequence Myocardium rat model Cell Membrane lcsh:R medicine.disease Actin cytoskeleton musculoskeletal system becker muscular dystrophy Rats Muscular Dystrophy Duchenne Disease Models Animal Endocrinology Phenotype Mutation biology.protein Dystrophin Research Article lcsh:RB1-214 |
| Zdroj: | Disease Models & Mechanisms, Vol 13, Iss 9 (2020) Disease Models & Mechanisms article-version (VoR) Version of Record |
| ISSN: | 1754-8411 1754-8403 |
| Popis: | Dystrophin, encoded by the DMD gene on the X chromosome, stabilizes the sarcolemma by linking the actin cytoskeleton with the dystrophin-glycoprotein complex (DGC). In-frame mutations in DMD cause a milder form of X-linked muscular dystrophy, called Becker muscular dystrophy (BMD), characterized by the reduced expression of truncated dystrophin. So far, no animal model with in-frame mutations in Dmd has been established. As a result, the effect of in-frame mutations on the dystrophin expression profile and disease progression of BMD remains unclear. In this study, we established a novel rat model carrying in-frame Dmd gene mutations (IF rats) and evaluated the pathology. We found that IF rats exhibited reduced expression of truncated dystrophin in a proteasome-independent manner. This abnormal dystrophin expression caused dystrophic changes in muscle tissues but did not lead to functional deficiency. We also found that the expression of additional dystrophin named dpX, which forms the DGC in the sarcolemma, was associated with the appearance of truncated dystrophin. In conclusion, the outcomes of this study contribute to the further understanding of BMD pathology and help elucidate the efficiency of dystrophin recovery treatments in Duchenne muscular dystrophy, a more severe form of X-linked muscular dystrophy. Editor's choice: The newly established rat model carrying in-frame mutations in the Dmd gene exhibits the dystrophic phenotype and abnormal dystrophin expression profile, similar to patients with Becker muscular dystrophy. |
| Databáze: | OpenAIRE |
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