Mait Carre-Pierrat1, Karine Grisoni1, Kathrin Gieseler1, Marie-Christine Mariol1, Edwige Martin1, Maelle Jospin2, Bruno Allard2 and Laurent Sgalat1. Duchenne Muscular Dystrophy (DMD) is a human disease caused by the absence of dystrophin in the skeletal muscles. It is characterized by a progressive muscular degeneration that leads to paralysis and death. Mutations in the Caenorhabditis elegans homologue of the dystrophin gene,
dys-1, lead to a peculiar phenotype of head-bending and hyperactivity. By mutating
dys-1 in a sensitized background
hlh-1(
cc561), we have developed a model of progressive muscular degeneration in C. elegans. We use this model to investigate the mechanisms of dystrophin-dependent muscular degeneration..
slo-1 encodes a large conductance BK calcium-activated potassium channel, SLO-1, that is expressed in C. elegans neurons and muscle cells. It was previously shown to be involved in neurotransmitter release. New
slo-1 alleles were isolated in our lab in a search for
dys-1-like mutants. When put in the
hlh-1(
cc561) background,
slo-1 mutations also lead to a progressive muscle degeneration.. We showed that it is the loss of the muscular form of SLO-1, and not the neuronal form, that leads to
dys-1-like phenotypes. SLO-1 localization was observed by gfp reporter in C. elegans body wall muscle cells, where it seems to co-localize partly with dystrophin in dense bodies.. Finally, we recorded SLO-1 activity on body wall muscle cells using the inside-out configuration of the patch clamp technique. As previously established, SLO-1 channels were selective for K+ and their opening was reversibly inhibited by removal of internal Ca2+. Neither the abundance nor the conductance of SLO-1 were significantly changed in
dys-1 mutants compared to wild-type animals. These results indicate that SLO-1 function in C. elegans muscle cells is related to dystrophin. Our working model is that the inactivation of
dys-1 causes a misregulation of SLO-1, which in turn may contribute to the pathogenecity of
dys-1 mutations.