Mutations in the C.elegans Dystrophin/Utrophin homolog encoding
dys-1 gene, present with hyper-sensitivity to Aldicarb and Levamisole induced paralysis, Serotonin resistance, as well as increased thrashing. These phenotypes cumulatively suggest a role for the DYS-1 protein in neuro-muscular excitation. Behavioral studies, as well as worm tracking experiments, suggest that
dys-1 mutants have altered sinusoidal coordination similar to GABA mutants. We have undertaken genetic studies, and Immuno-histochemistry to define the perturbation in synaptic transmission. Moreover, we have constructed tissue specific RNAi constructs to define previously uncharacterized DYS-1 pre-synaptic function. The
dys-1 mutants exhibit no gross malformations in sub-cellular muscular components including the cytoskeleton; however, when
dys-1 mutants are placed in a sensitized
hlh-1/MYO-D mutant background, the worm displays progressive deterioration of muscle cell structures including organelles and cytoskeletal elements, which ultimately leads to cell death. This pathogenic process can be re-capitulated by placing mutations with altered synaptic transmission, into the sensitized
hlh-1/MYO-D background. We speculate that the perturbation of synaptic transmission, associated with the mutation of
dys-1, contributes to the muscle degenerative phenotype viewed in the
dys-1;
hlh-1 double mutant.