Fragile skeletal muscle attachments in dystrophic mutants of Caenorhabditis elegans: isolation and characterization of the mua genes

Over 30 Caenorhabditis elegans mutants were identified with normal muscle d ifferentiation and initial locomotion followed by catastrophic detachment o f skeletal muscles from the body wall. Reducing the strength of muscle cont raction in these mutants with a myosin gene mutation suppresses muscle deta chment. These dystrophic mutants identify a novel class of genes required f or growth and maintenance of functional muscle attachments, not exceptional alleles of genes required for muscle differentiation and contractility. Ni ne new genes, named mua, and two previously published loci, unc-23 and vab- 10, cause fragile muscle attachments. The primary sites of muscle detachmen t, including the plane of tissue separation, are characteristic for each ge ne. We suggest these genes identify feedback mechanisms whereby local strai n regulates the extent of myofibril contraction and the placement of new mu scle attachments in functioning muscles. Finally, we draw some comparisons to vertebrate skin fragility diseases and muscular dystrophies.