The Zzzz\CTG250.Scer\UAS.cCa model recapitulates the heart dysfunction often seen in DM1.
Expression of Zzzz\CTG250.Scer\UAS.cCa under the control of Scer\GAL4Mhc.PW leads to decreased adult lifespan, defects in adult locomotion (climbing or flight abilities) and reduced indirect flight muscles area in either 3-day or 30-day-old flies relative to age-matched controls, moreover vacuolization and muscle splitting is observed in the aged flies. Scer\GAL4tin.cBa-driven expression also reduces adult lifespan and it induces cardiac function defects (increased heart period, prolonged both diastolic and systolic intervals, reduced heart tube contractility and increased arrhythmia), but adult locomotion (either climbing or flight) is not significantly affected.
One week-old flies expressing Zzzz\CTG20.Scer\UAS.cCa under the control of Scer\GAL4tin.cBa and Scer\GAL4Scer\UAS.cHa (collectively known as GMH5-Gal4) show abnormalities in the parallel alignment of transverse myofibrils compared to controls. Heart contractions are arrhythmic and morphological constrictions are seen in small regions along the heart tube where no relaxation phase is observed. The heart period length (diastolic plus systolic interval) is significantly increased compared with control flies. Heart rate is increased and both systolic interval and diastolic interval are significantly prolonged compared with controls. There is a significant decrease in end diastolic diameter (EDD) and a reduced percentage of fractional shortening (FS). Feeding the flies with pentamidine significantly rescues the reduction in lifespan and arrhythmicity. Pentamidine does not modify heart rate, diastolic interval, systolic interval nor end diastolic diameter, but strongly reduces end systolic diameter.