Collagen VI deficiency reduces muscle pathology, but does not improve muscle function, in the γ-sarcoglycan-null mouse
| Autor: | Braden S. Jensen, Raul O’Campo Landa, Jennifer R. Levy, Jessica C. de Greef, Kazuhiro Kobuke, Rebecca Hamlyn, Kevin P. Campbell |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine medicine.medical_specialty Down-Regulation Collagen Type VI Biology Skeletal muscle fibrosis Mice 03 medical and health sciences Collagen VI Internal medicine Sarcoglycanopathies Genetics medicine Animals Myocyte Muscular dystrophy Muscle Skeletal Molecular Biology Genetics (clinical) Muscle contracture Mice Knockout Skeletal muscle Articles General Medicine Anatomy Muscular Dystrophy Animal medicine.disease Sarcoglycan 030104 developmental biology medicine.anatomical_structure Endocrinology ITGA7 |
| Zdroj: | Human Molecular Genetics |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddw018 |
| Popis: | Muscular dystrophy is characterized by progressive skeletal muscle weakness and dystrophic muscle exhibits degeneration and regeneration of muscle cells, inflammation and fibrosis. Skeletal muscle fibrosis is an excessive deposition of components of the extracellular matrix including an accumulation of Collagen VI. We hypothesized that a reduction of Collagen VI in a muscular dystrophy model that presents with fibrosis would result in reduced muscle pathology and improved muscle function. To test this hypothesis, we crossed γ-sarcoglycan-null mice, a model of limb-girdle muscular dystrophy type 2C, with a Col6a2-deficient mouse model. We found that the resulting γ-sarcoglycan-null/Col6a2Δex5 mice indeed exhibit reduced muscle pathology compared with γ-sarcoglycan-null mice. Specifically, fewer muscle fibers are degenerating, fiber size varies less, Evans blue dye uptake is reduced and serum creatine kinase levels are lower. Surprisingly, in spite of this reduction in muscle pathology, muscle function is not significantly improved. In fact, grip strength and maximum isometric tetanic force are even lower in γ-sarcoglycan-null/Col6a2Δex5 mice than in γ-sarcoglycan-null mice. In conclusion, our results reveal that Collagen VI-mediated fibrosis contributes to skeletal muscle pathology in γ-sarcoglycan-null mice. Importantly, however, our data also demonstrate that a reduction in skeletal muscle pathology does not necessarily lead to an improvement of skeletal muscle function, and this should be considered in future translational studies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|