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Fig. 4. | BMC Biology

Fig. 4.

From: Unexpected cell type-dependent effects of autophagy on polyglutamine aggregation revealed by natural genetic variation in C. elegans

Fig. 4.

Hypermorphic variants in the autophagy gene atg-5 are responsible for the increased polyQ aggregation in the body-wall muscles. a PolyQ aggregation in the body-wall muscles is sensitive to the dosage of the drxlR1 interval, with DR1350-derived interval acting as a hypermorph relative to the Bristol-derived interval. Each symbol represents an individual mid-L4 animal; overlaid are means ± SD. Schematic under the graph represents the genetic composition of chromosome I: Bristol background (orange bar), DR1350-derived drxlR1 interval (red arrow), and the free duplication sDp2 (green bar). b RNAi of three candidate genes affects polyQ40 aggregation. atg-5 RNAi suppresses the increased polyQ aggregation in the muscle cells of drxlR1 but not in Q40Bristol animals. RNAi against YFP downregulates expression of Q40::YFP protein. Data are mean ± SD, 3 independent experiments, 9 to 15 animals per experiment per genotype. Data were analyzed by ANOVA followed by Bonferroni’s multiple comparisons test, ****P < 0.0001, **P = 0.0029, *P = 0.0125. c Relative expression of atg-5 mRNA is unaffected by the DR1350-derived drxIR1 interval. Three independent experiments, statistics as in b. d atg-5(bp484) loss-of-function allele reverses increased aggregation caused by one copy of the DR1350-derived drxIR1 interval. Schematic under the graph as in a, star: atg-5 mutation. Animals were scored at mid-L4 as in a, compare drxIR1/+;Q40 animals (red/orange symbols) in a with drxIR1/atg-5;Q40 animals (red/gray symbols) in d. Gray symbols represent animals that were assumed (but not confirmed) to be heterozygous for the drxIR1 interval, because they did not show the RIL2-like phenotype head muscle phenotype and because atg-5/atg-5 animals exhibit strong developmental delay. Heterozygosity of drxIR1/atg-5;Q40 animals (red/gray symbols) was confirmed by singling them out and scoring segregation of the RIL2-like phenotype among their progeny. Each symbol represents an individual animals, overlaid are means ± SD

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