Mitochondrial abnormalities contribute to muscle weakness in a Dnajb6 deficient zebrafish model.
Hum Mol Genet
; 33(14): 1195-1206, 2024 Jul 06.
Article
en En
| MEDLINE
| ID: mdl-38621658
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pez Cebra
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Chaperonas Moleculares
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Debilidad Muscular
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Distrofia Muscular de Cinturas
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Modelos Animales de Enfermedad
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Proteínas del Choque Térmico HSP40
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Mitocondrias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Australia