The myotendinous junction (MTJ) is essential for the integrity of the musculoskeletal unit. Here, we show that gene ablation of the MTJ marker col22a1 in zebrafish results in MTJ dysfunction but with variable degrees of expression and distinct phenotypic classes. While most individuals reach adulthood with no overt muscle phenotype (class 1), a subset of the progeny displays severe movement impairment and die before metamorphosis (class 2). Yet all mutants display muscle weakness due to ineffective muscle force transmission that is ultimately detrimental for class-specific locomotion-related functions. Movement impairment at the critical stage of swimming postural learning causes class 2 larval death by compromising food intake. In class 1 adults, intensive exercise is required to uncover a decline in muscle performance, accompanied by higher energy demand and mitochondrial adaptation. This study underscores COL22A1 as a candidate gene for myopathies associated with dysfunctional force transmission and anticipates a phenotypically heterogeneous disease.

肌腱接头 (MTJ) 对于肌肉骨骼单元的完整性至关重要。在这里，我们展示了 MTJ 标记col22a1的基因消融在斑马鱼中导致 MTJ 功能障碍，但具有不同程度的表达和不同的表型类别。虽然大多数人成年后没有明显的肌肉表型（1 类），但后代的一部分表现出严重的运动障碍并在变态前死亡（2 类）。然而，由于无效的肌肉力量传递，所有突变体都表现出肌肉无力，这最终对特定类别的运动相关功能有害。游泳姿势学习关键阶段的运动障碍通过影响食物摄入量导致 2 级幼虫死亡。在 1 级成人中，需要进行剧烈运动才能发现肌肉性能下降，同时伴随着更高的能量需求和线粒体适应。这项研究强调了COL22A1作为与功能障碍性力传递相关的肌病的候选基因，并预测一种表型异质性疾病。