[PhD Thesis Presentation] ‐Kazuto Kawamura‐ Forward genetic screen for Caenorhabditis elegans mutants with a progressive decline in adult locomotor function

Abstract
Some inherited mutations can cause a delayed onset of toxic symptoms. These types of mutations can be the underlying cause of age-related diseases or more prevalent agerelated functional impairments. The isolation of mutants and identification of mutations in model organisms that show delayed onset of toxic symptoms may provide insights into evolutionarily conserved genetic regulators that function during the maintenance of functional capacities. In this study, we carried out an unbiased forward genetic screen for Caenorhabditis elegans mutants that show progressive loss of locomotor function during adulthood. After screening 3,352 F2 worms from 1,000 haploid genomes, we isolated five mutant strains that progressively lose their ability to complete a locomotor assay. For one of the mutant strains, a nonsense mutation in Elongator Complex Protein Component 2 (elpc-2) causes the progressive decline in locomotor function. Other C. elegans mutants with mutations in subunits of the Elongator complex also showed progressive declines in adult locomotor function. The Elongator complex may play a critical role during the maintenance of adult locomotor function in C. elegans. The screening procedure, isolated mutants, and the Elongator complex are valuable tools to further explore how locmotor healthspan is maintained in animals.