{'fraction_non_alphanumeric': 0.017204301075268817, 'fraction_numerical': 0.0, 'mean_word_length': 5.78134110787172, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle

Significance Dystroglycan (DG) is an extracellular matrix receptor that is linked to the cytoskeleton and critical for the development of skeletal muscle. DG deficiency throughout development is associated with multiple pathological features and muscular dystrophy. However, the direct consequence of DG disruption in mature muscle is not known. Here, we investigate muscles of transgenic mice after genetic knockdown of DG at maturity. The results demonstrate early susceptibility to contraction-induced injury accompanied by reduced passive tension and decreased titin immunostaining, rather than increased necrosis, excitation–contraction uncoupling, or sarcolemmal fragility. These results suggest a need for critical rethinking of both current theories regarding contraction-induced injury in muscular dystrophy and therapeutic strategies. Dystroglycan (DG) is a highly expressed extracellular matrix receptor that is linked to the cytoskeleton in skeletal muscle. DG is critical for the function of skeletal muscle, and muscle with primary defects in the expression and/or function of DG throughout development has many pathological features and a severe muscular dystrophy phenotype. In addition, reduction in DG at the sarcolemma is a common feature in muscle biopsies from patients with various types of muscular dystrophy. However, the consequence of disrupting DG in mature muscle is not known. Here, we investigated muscles of transgenic mice several months after genetic knockdown of DG at maturity. In our study, an increase in susceptibility to contraction-induced injury was the first pathological feature observed after the levels of DG at the sarcolemma were reduced. The contraction-induced injury was not accompanied by increased necrosis, excitation–contraction uncoupling, or fragility of the sarcolemma. Rather, disruption of the sarcomeric cytoskeleton was evident as reduced passive tension and decreased titin immunostaining. These results reveal a role for DG in maintaining the stability of the sarcomeric cytoskeleton during contraction and provide mechanistic insight into the cause of the reduction in strength that occurs in muscular dystrophy after lengthening contractions.