Publication Date:
2012-08-28
Description:
Myofibrillar myopathies are a group of muscle disorders characterized by the disintegration of skeletal muscle fibers and formation of sarcomeric protein aggregates. All the proteins known to be involved in myofibrillar myopathies localize to a region of the sarcomere known as the Z-disk, the site at which defects are first observed. Given the common cellular phenotype observed in this group of disorders, it is thought that there is a common mechanism of pathology. Mutations in filamin C, which has several proposed roles in the development and function of skeletal muscle, can result in filamin-related myofibrillar myopathy. The lack of a suitable animal model system has limited investigation into the mechanism of pathology in this disease and the role of filamin C in muscle development. Here, we characterize stretched out ( sot ), a zebrafish filamin Cb mutant, together with targeted knockdown of zebrafish filamin Ca , revealing fiber dissolution and formation of protein aggregates strikingly similar to those seen in filamin-related myofibrillar myopathies. Through knockdown of both zebrafish filamin C homologues, we demonstrate that filamin C is not required for fiber specification and that fiber damage is a consequence of muscle activity. The remarkable similarities in the myopathology between our models and filamin-related myofibrillar myopathy makes them suitable for the study of these diseases and provides unique opportunities for the investigation of the function of filamin C in muscle and development of therapies.
Print ISSN:
0964-6906
Electronic ISSN:
1460-2083
Topics:
Biology
,
Medicine
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