MUTATIONS IN THE UNC-52 GENE RESPONSIBLE FOR BODY-WALL MUSCLE DEFECTSIN ADULT CAENORHABDITIS-ELEGANS ARE LOCATED IN ALTERNATIVELY SPLICED EXONS

The unc-52 gene in Caenorhabditis elegans produces several large prote ins that function in the basement membrane underlying muscle cells. Mu tations in this gene result in defects in myofilament assembly and in the attachment of the myofilament lattice to the muscle cell membrane. The st549 and ut111 alleles of unc-52 produce a lethal (Pat) terminal phenotype whereas the c444, e669, e998, e1012 and e1421 mutations res ult in viable, paralyzed animals. We have identified the sequence alte rations responsible for these mutant phenotypes. The st549 allele has a premature stop codon in exon 7 that should result in the complete el imination of unc-52 gene function, and the ut111 allele has a Tc1 tran sposon inserted into the second exon of the gene. The five remaining m utations are clustered in a small interval containing three adjacent, alternatively spliced exons (16, 17 and 18). These mutations affect so me, but not all of the unc-52-encoded proteins. Thirteen intragenic re vertants of the e669, e998, e1012 and e1421 alleles have also been seq uenced. The majority of these carry the original mutation plus a G to A transition in the conserved splice acceptor site of the affected exo n. This result suggests that reversion of the mutant phenotype in thes e strains may be the result of exon-skipping.