RT Journal Article
SR Electronic
T1 The myotendinous junction marker collagen XXII enables zebrafish postural control learning and optimal swimming performance through its force transmission activity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.14.452354
DO 10.1101/2021.07.14.452354
A1 Malbouyres, Marilyne
A1 Guiraud, Alexandre
A1 Lefrançois, Christel
A1 Salamito, Mélanie
A1 Nauroy, Pauline
A1 Bernard, Laure
A1 Sohm, Frédéric
A1 Allard, Bruno
A1 Ruggiero, Florence
YR 2021
UL http://biorxiv.org/content/early/2021/07/15/2021.07.14.452354.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.