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Functional Characterization of the Adenylyl Cyclase Gene sgs-1 by Analysis of a Mutational Spectrum in Caenorhabditis elegans
Celine Moormana and Ronald H. A. Plasterkaa Hubrecht Laboratory, Centre for Biomedical Genetics, 3584 CT, Utrecht, The Netherlands
Corresponding author: Ronald H. A. Plasterk, Centre for Biomedical Genetics, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands., plasterk{at}niob.knaw.nl (E-mail)
Communicating editor: P. ANDERSON
s) gene encodes one of the four adenylyl cyclases in the nematode C. elegans and is most similar to mammalian adenylyl cyclase type IX. We isolated a complete loss-of-function mutation in sgs-1 and found it to result in animals with retarded development that arrest in variable larval stages. sgs-1 mutant animals exhibit lethargic movement and pharyngeal pumping and (while not reaching adulthood) have a mean life span that is >50% extended compared to wild type. An extensive set of reduction-of-function mutations in sgs-1 was isolated in a screen for suppressors of a neuronal degeneration phenotype induced by the expression of a constitutively active version of the heterotrimeric Gs subunit of C. elegans. Although most of these mutations change conserved residues within the catalytic domains of sgs-1, mutations in the less-conserved transmembrane domains are also found. The sgs-1 reduction-of-function mutants are viable and have reduced locomotion rates, but do not show defects in pharyngeal pumping or life span.
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