PUBLICATION
Mitochondrial abnormalities contribute to muscle weakness in a Dnajb6 deficient zebrafish model
- Authors
- McKaige, E.A., Lee, C., Calcinotto, V., Giri, S., Crawford, S., McGrath, M.J., Ramm, G., Bryson-Richardson, R.J.
- ID
- ZDB-PUB-240416-26
- Date
- 2024
- Source
- Human molecular genetics 33(14): 1195-1206 (Journal)
- Registered Authors
- Bryson-Richardson, Robert, Calcinotto, Vanessa, Lee, Clara, McKaige, Emily
- Keywords
- disease model, dnajb6, mitochondria, myopathy, zebrafish
- MeSH Terms
-
- Muscular Dystrophies, Limb-Girdle*/genetics
- Muscular Dystrophies, Limb-Girdle*/metabolism
- Muscular Dystrophies, Limb-Girdle*/pathology
- HSP40 Heat-Shock Proteins*/genetics
- HSP40 Heat-Shock Proteins*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Muscle Weakness*/genetics
- Muscle Weakness*/metabolism
- Muscle Weakness*/pathology
- Disease Models, Animal*
- Humans
- Molecular Chaperones*/genetics
- Molecular Chaperones*/metabolism
- Nerve Tissue Proteins
- Muscle, Skeletal/metabolism
- Muscle, Skeletal/pathology
- Muscle, Skeletal/physiopathology
- Animals
- Mutation
- Zebrafish*/genetics
- Autophagy/genetics
- Mitochondria*/genetics
- Mitochondria*/metabolism
- Mitochondria*/pathology
- PubMed
- 38621658 Full text @ Hum. Mol. Genet.
Citation
McKaige, E.A., Lee, C., Calcinotto, V., Giri, S., Crawford, S., McGrath, M.J., Ramm, G., Bryson-Richardson, R.J. (2024) Mitochondrial abnormalities contribute to muscle weakness in a Dnajb6 deficient zebrafish model. Human molecular genetics. 33(14):1195-1206.
Abstract
Mutations in DNAJB6 are a well-established cause of limb girdle muscular dystrophy type D1 (LGMD D1). Patients with LGMD D1 develop progressive muscle weakness with histology showing fibre damage, autophagic vacuoles, and aggregates. Whilst there are many reports of LGMD D1 patients, the role of DNAJB6 in the muscle is still unclear. In this study, we developed a loss of function zebrafish model in order to investigate the role of Dnajb6. Using a double dnajb6a and dnajb6b mutant model, we show that loss of Dnajb6 leads to a late onset muscle weakness. Interestingly, we find that adult fish lacking Dnajb6 do not have autophagy or myofibril defects, however, they do show mitochondrial changes and damage. This study demonstrates that loss of Dnajb6 causes mitochondrial defects and suggests that this contributes to muscle weakness in LGMD D1. These findings expand our knowledge of the role of Dnajb6 in the muscle and provides a model to screen novel therapies for LGMD D1.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping