UAS regulatory sequences drive expression of a dsRNA that targets sequence specific to the Dp117 isoform of Dys (the dsRNA consists of an inverted repeat of nucleotides 749-1288 of the Dp117 isoform, accession number GB:NM142555, with the repeats separated by a spacer consisting of mub intron sequence).
Animals expressing DysdsRNA.Dp117.Scer\UAS RNAi under the control of Scer\GAL4how-24B die as white pupae. When two copies of the RNAi transgene are used, the animals die as larvae - arrested at early third instar. The food uptake of these larvae is normal during first two instars but they cease to feed completely during the third, excretion is not affected and neither is heart function.
Survival rates of animals expressing two copies of DysdsRNA.Dp117.Scer\UAS under the control of any of the following: Scer\GAL4elav.PLu, Scer\GAL4Hand.PA, Scer\GAL4tin.CΔ4, Scer\GAL4bap.3 or Scer\GAL4drm.7.1 are comparable to wild-type, expression under the Scer\GAL4Mhc.PW driver leads to only moderately increased pupal lethality.
DysdsRNA.Dp117.Scer\UAS RNAi under the control of Scer\GAL4how-24B results in increased proportion of third instar larvae showing muscle degeneration defects compared to controls (the effect was stronger when two copies of the DysdsRNA.Dp117.Scer\UAS transgene were used); embryonic musculature was unaffected. Expression of single copy under the Scer\GAL4Mef2.PR leads to moderate increase in the levels of muscle damage observed in third instar larvae compared to wild-type, while the damage seen when the Scer\GAL4Mhc.PW driver is used is only slightly higher.
No additive effect in the severity or penetrance of the muscle degeneration phenotype is observed in third instar larvae expressing single copy of DysdsRNA.Dp117.Scer\UAS RNAi driven by Scer\GAL4Mef2.PR in the DysE6 homozygous background, compared to the DysdsRNA.Dp117.Scer\UAS expressing-only animals.
Actin organization in the third instar larval muscles is disrupted in animals expressing two copies of DysdsRNA.Dp117.Scer\UAS RNAi under the control of Scer\GAL4how-24B but the T-tubular structure is not affected.
Expression of one or two copies of DysdsRNA.Dp117.Scer\UAS under the control of Scer\GAL4how-24B results signs of muscle necrosis in third instar larvae manifested on the ultrastructural level mostly by swollen mitochondria and sarcoplasmic reticulum, disorganized actin-myosin filaments.
Pharate adults expressing two copies of DysdsRNA.Dp117.Scer\UAS under the control of Scer\GAL4Mef2.PR display myofibrils of smaller diameter compared to wild-type.