Myotonic Dystrophy is an inherited, autosomal dominant disease that results in a progressive wasting of the skele- tal muscles (and sometimes heart and smooth muscles) in humans. The gene has been cloned and sequenced (R. Korneluk, personal communication) and encodes a large protein that has been localised to neuromuscular and myotendinous junctions. The N-terminus domain bears similarity to cAMP-dependent serine/threonine protein kinases. Yuji Kohara, in his cDNA sequencing project, identified a C. elegans gene that is 75% similar (if conserved amino acids are considered) to the kinase domain of the human myotonic dystrophy gene. He mapped the cDNA to LG I (personal communication), and, through Southern analysis, we have placed the cDNA on cosmid K06G1. This cosmid was injected into wild-type N2 hermaphrodites by Diana Collins, and we are currently trying to rescue some of the genes in this region with the extrachromosomal array. One candidate gene was
unc-57. Animals homozygous for mutations in
unc-57 show no obvious structural muscle defects. This is consistent with
unc-57 being a muscle, or neuro- muscular kinase. However, the Unc-57 phenotype is not rescued in animals carrying the K06G1 extrachromo- somal array. We are now focusing on some of the lethal mutations in this region that have been isolated in the laboratory of Ann Rose at UBC.