The myotendinous junction marker collagen XXII enables zebrafish postural control learning and optimal swimming performance through its force transmission activity
| Autor: | Sohm F, Allard B, Alexandre Guiraud, Lefrancois C, Malbouyres M, Bernard L, Pauline Nauroy, Salamito M, Florence Ruggiero |
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| Přispěvatelé: | Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon), Université de La Rochelle (ULR), Plateforme d'ingénierie génétique des animaux modèles (AMAGEN), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Ampère, Département Energie Electrique (EE), Ampère (AMPERE), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) |
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Candidate gene biology [SDV]Life Sciences [q-bio] Mutant Skeletal muscle Muscle weakness biology.organism_classification Phenotype 03 medical and health sciences [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis 0302 clinical medicine medicine.anatomical_structure Gene expression medicine medicine.symptom [SDV.BDD]Life Sciences [q-bio]/Development Biology Neuroscience Zebrafish Gene 030217 neurology & neurosurgery 030304 developmental biology |
| DOI: | 10.1101/2021.07.14.452354 |
| Popis: | Although the myotendinous junction (MTJ) is essential for skeletal muscle integrity, its contribution to skeletal muscle function remains largely unknown. Here, we show that CRISPR-Cas9-mediated gene ablation of the MTJ marker col22a1 in zebrafish identifies two distinctive phenotypic classes: class 1 individuals reach adulthood with no overt muscle phenotype while class 2 display severe movement impairment and eventually dye before metamorphosis. Yet mutants that are unequally affected are all found to display defective force transmission attributed to a loss of ultrastructural integrity of the MTJ and myosepta, though with distinct degrees of severity. The behavior-related consequences of the resulting muscle weakness similarly reveal variable phenotypic expressivity. Movement impairment at the critical stage of swimming postural learning eventually causes class 2 larval death by compromising food intake while intensive exercise is required to uncover a decline in muscle performance in class 1 adults. By confronting MTJ gene expression compensation and structural, functional and behavioral insights of MTJ dysfunction, our work unravels variable expressivity of col22a1 mutant phenotype. This study also underscores COL22A1 as a candidate gene for myopathies associated with dysfunctional force transmission and anticipates a phenotypically heterogeneous disease. |
| Databáze: | OpenAIRE |
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