Research Paper Advance Articles pp 23525—23547

Mutation in histone deacetylase HDA-3 leads to shortened locomotor healthspan in Caenorhabditis elegans

Figure 1. OF1262 strain shows locomotor deficit and carries hda-3(ix241) and dys-1(ix259) mutations. (A) Schematic of forward genetic screen to isolate OF1262 strain, a strain that shows progressive decline in adult motility. (B) Percent change in completion rate of the Edge Assay on adult day 5 compared to adult day 1. N = 3 biological replicate plates (100 worms or more per plate on adult day 1). (C) Mutation frequency along each chromosome for the OF1262 strain. Red bars indicate 0.5-Mb bins and grey bars indicate 1.0-Mb bins. (D) Mutation frequency along each chromosome for remaining mutations after subtracting mutations found in backcrossed strains that did not show a progressive decline in locomotor ability from mutations found in backcrossed strains that showed a progressive decline in locomotor ability. (E) Effect of hda-3(ix241) mutation on DNA sequence and amino acid sequence. (F) Effect of dys-1(ix259) mutation on DNA sequence. (G) Photos of head curvature during forward crawling in WT, dys-1(cx18) and dys-1(eg33) worms. Exaggerated head bending indicated by arrows. (H) (Top) Photo of head curvature during forward crawling in OF1350 dys-1(ix259) worms. (Bottom) DNA sequence of dys-1(ix259) mutation site. (I) (Left) Maximum velocities of WT, OF1263 hda-3(ix241);dys-1(ix259) (4x BC), and OF1350 dys-1(ix259) (5x BC) worms. N = 30–45 worms per strain for each day (10–15 worms from 3 biological replicate plates). (Right) Percent change in maximum velocity of WT, OF1263, and OF1350 worms on adult day 5 compared to adult day 1. N = 3 biological replicate plates. ***p < 0.001; **p < 0.01.