Fig. 5.

Reduced or no dystrophin-like products (DLPs) causes dilated cardiomyopathy in the adult Drosophila heart. (A) Two-segment image of a 1-week-old wild-type (wt) heart in systole (top) and diastole (bottom). (B) 1-week-old dysExel6184/dyskx43 heart in systole and diastole. Note that both diastolic and systolic diameters are wider in the DLPs-deficient mutants compared to wt. Arrowheads indicate the heart wall in both phases of the cardiac cycle. (C–E) Heart parameters in wt and dys mutants. (C,D) dysExel6184/dyskx43 and dys^8-2/dyskx43 mutants have a larger systolic (C) and diastolic diameters (D) than the wt at all ages. Significant differences were determined by t-test. P values < 0.05 were considered significant (*P < 0.0001). (E) Plot of fractional shortening for the wt and dys mutants. dysExel6184/dyskx43 shows lower fractional shortening at all ages, whereas dys^8-2/dyskx43 mutants only at 3 weeks or older (*P < 0.001, except dys^8-2/dyskx43 at 7 weeks is P < 0.05). Movies were taken from 15 to 20 flies for each genotype. (F, G) Rescue of dysExel6184/dyskx43 mutants by the mammalian short dys isoform Dp116. Mesodermal expression of Dp116 restores the dilated systolic diameter (F) and the reduced fractional shortening to near normal (G). The Dp116 transgene was driven by the mesodermal driver 24B-GAL4 in the dys mutant background (Dp116/+; dyskx43/dysExel6184,24B). Cardiac function evaluated in 1-week-old rescue dys mutants shows a normalization of the systolic dysfunction (F, G) (*P < 0.01 by t-test assuming equal variances). For the genotype Dp116/+; dyskx43/dysExel6184,24B measurements (± standard error) were derived from movies of 20 flies. Similar rescue as with 1-week-old flies was observed in 3-week-old flies (data not shown).