دورية أكاديمية
Respiratory characterization of a humanized Duchenne muscular dystrophy mouse model.
| العنوان: | Respiratory characterization of a humanized Duchenne muscular dystrophy mouse model. |
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| المؤلفون: | Roger AL; Department of Pediatrics, Duke University, Durham, NC, USA., Biswas DD; Department of Pediatrics, Duke University, Durham, NC, USA., Huston ML; Department of Pediatrics, Duke University, Durham, NC, USA., Le D; Department of Pediatrics, Duke University, Durham, NC, USA., Bailey AM; Department of Pediatrics, Duke University, Durham, NC, USA., Pucci LA; Department of Pediatrics, Duke University, Durham, NC, USA., Shi Y; Department of Pediatrics, Duke University, Durham, NC, USA., Robinson-Hamm J; Department of Biomedical Engineering, Duke University, Durham, NC, USA., Gersbach CA; Department of Biomedical Engineering, Duke University, Durham, NC, USA., ElMallah MK; Department of Pediatrics, Duke University, Durham, NC, USA. Electronic address: mai.elmallah@duke.edu. |
| المصدر: | Respiratory physiology & neurobiology [Respir Physiol Neurobiol] 2024 Aug; Vol. 326, pp. 104282. Date of Electronic Publication: 2024 May 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 101140022 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1519 (Electronic) Linking ISSN: 15699048 NLM ISO Abbreviation: Respir Physiol Neurobiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2002- |
| مواضيع طبية MeSH: | Muscular Dystrophy, Duchenne*/genetics , Muscular Dystrophy, Duchenne*/pathology , Muscular Dystrophy, Duchenne*/physiopathology , Disease Models, Animal* , Mice, Transgenic*, Animals ; Mice ; Humans ; Male ; Dystrophin/genetics ; Dystrophin/deficiency ; Mice, Inbred mdx ; Diaphragm/physiopathology ; Diaphragm/pathology ; Respiratory Insufficiency/etiology ; Neuromuscular Junction/pathology ; Neuromuscular Junction/metabolism ; Mice, Inbred C57BL |
| مستخلص: | Duchenne muscular dystrophy (DMD) is the most common X-linked disease. DMD is caused by a lack of dystrophin, a critical structural protein in striated muscle. Dystrophin deficiency leads to inflammation, fibrosis, and muscle atrophy. Boys with DMD have progressive muscle weakness within the diaphragm that results in respiratory failure in the 2nd or 3rd decade of life. The most common DMD mouse model - the mdx mouse - is not sufficient for evaluating genetic medicines that specifically target the human DMD (hDMD) gene sequence. Therefore, a novel transgenic mouse carrying the hDMD gene with an exon 52 deletion was created (hDMDΔ52;mdx). We characterized the respiratory function and pathology in this model using whole body plethysmography, histology, and immunohistochemistry. At 6-months-old, hDMDΔ52;mdx mice have reduced maximal respiration, neuromuscular junction pathology, and fibrosis throughout the diaphragm, which worsens at 12-months-old. In conclusion, the hDMDΔ52;mdx exhibits moderate respiratory pathology, and serves as a relevant animal model to study the impact of novel genetic therapies, including gene editing, on respiratory function. Competing Interests: Declaration of Competing Interest CAG is an advisor to Sarepta Therapeutics and an advisor and co-founder of Tune Therapeutics. CAG and JRH are inventors on patents and patent applications related to genome editing. AMB is an employee and stakeholder of Fulcrum Therapuetics. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Diaphragm; Duchenne; Fibrosis; Respiratory; Tongue |
| المشرفين على المادة: | 0 (Dystrophin) 0 (DMD protein, human) |
| تواريخ الأحداث: | Date Created: 20240523 Date Completed: 20240609 Latest Revision: 20240609 |
| رمز التحديث: | 20240610 |
| DOI: | 10.1016/j.resp.2024.104282 |
| PMID: | 38782084 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1878-1519 |
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| DOI: | 10.1016/j.resp.2024.104282 |