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Absence of microRNA-21 does not reduce muscular dystrophy in mouse models of LAMA2-CMD
Absence of microRNA-21 does not reduce muscular dystrophy in mouse models of LAMA2-CMD
- Source :
- PLoS ONE, Vol 12, Iss 8, p e0181950 (2017), PLoS ONE
- Publication Year :
- 2017
- Publisher :
- Public Library of Science (PLoS), 2017.
-
Abstract
- MicroRNAs (miRNAs) are short non-coding RNAs that modulate gene expression post-transcriptionally. Current evidence suggests that miR-21 plays a significant role in the progression of fibrosis in muscle diseases. Laminin-deficient congenital muscular dystrophy (LAMA2-CMD) is a severe form of congenital muscular dystrophy caused by mutations in the gene encoding laminin α2 chain. Mouse models dy3K/dy3K and dy2J/dy2J, respectively, adequately mirror severe and milder forms of LAMA2-CMD. Both human and mouse LAMA2-CMD muscles are characterized by extensive fibrosis and considering that fibrosis is the final step that destroys muscle during the disease course, anti-fibrotic therapies may be effective strategies for prevention of LAMA2-CMD. We have previously demonstrated a significant up-regulation of the pro-fibrotic miR-21 in dy3K/dy3K and dy2J/dy2J skeletal muscle. Hence, the objective of this study was to explore if absence of miR-21 reduces fibrogenesis and improves the phenotype of LAMA2-CMD mice. Thus, we generated dy3K/dy3K and dy2J/dy2J mice devoid of miR-21 (dy3K/miR-21 and dy2J/miR-21 mice, respectively). However, the muscular dystrophy phenotype of dy3K/miR-21 and dy2J/miR-21 double knock-out mice was not improved compared to dy3K/dy3K or dy2J/dy2J mice, respectively. Mice displayed the same body weight, dystrophic muscles (with fibrosis) and impaired muscle function. These data indicate that miR-21 may not be involved in the development of fibrosis in LAMA2-CMD.
- Subjects :
- 0301 basic medicine
Male
Muscle Physiology
Physiology
lcsh:Medicine
Biochemistry
Muscular Dystrophies
Mice
Fibrosis
Gene expression
Morphogenesis
Medicine and Health Sciences
Muscular dystrophy
lcsh:Science
Musculoskeletal System
Mice, Knockout
Multidisciplinary
Muscles
Muscle Biochemistry
Anatomy
Animal Models
Phenotype
Nucleic acids
medicine.anatomical_structure
Experimental Organism Systems
Neurology
Congenital muscular dystrophy
Female
ITGA7
Muscle Regeneration
Research Article
medicine.medical_specialty
Mouse Models
Biology
Research and Analysis Methods
03 medical and health sciences
Model Organisms
Internal medicine
microRNA
medicine
Genetics
Regeneration
Animals
Non-coding RNA
Muscle, Skeletal
lcsh:R
Skeletal muscle
Biology and Life Sciences
Proteins
Muscular Dystrophy, Animal
medicine.disease
Gene regulation
Mice, Inbred C57BL
MicroRNAs
Disease Models, Animal
030104 developmental biology
Endocrinology
Skeletal Muscles
RNA
lcsh:Q
Laminin
Organism Development
Collagens
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....63770125de831ff614aeea2a91c4437d