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Respiratory characterization of a humanized Duchenne muscular dystrophy mouse model.
- Source :
-
Respiratory physiology & neurobiology [Respir Physiol Neurobiol] 2024 Aug; Vol. 326, pp. 104282. Date of Electronic Publication: 2024 May 21. - Publication Year :
- 2024
-
Abstract
- 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.<br />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.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- 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
Muscular Dystrophy, Duchenne genetics
Muscular Dystrophy, Duchenne pathology
Muscular Dystrophy, Duchenne physiopathology
Disease Models, Animal
Mice, Transgenic
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1519
- Volume :
- 326
- Database :
- MEDLINE
- Journal :
- Respiratory physiology & neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 38782084
- Full Text :
- https://doi.org/10.1016/j.resp.2024.104282