hangAE10 adult mutants exhibit reduced development of tolerance to ethanol exposure (increase in resistance upon re-exposition) as well as decreased heat-induced ethanol resistance normally observed in wild-type flies.
hangAE10 mutant flies show a normal initial mean elution time (MET) in an inebriometer, but have a reduced ability to develop tolerance to ethanol vapour compared to controls (14 +/- 3% increase in MET after pre-exposure to ethanol compared to an increase of 35 +/- 2% for control flies). The mutant flies also show defective ethanol tolerance in a chronic tolerance protocol in which flies are exposed to ethanol in the inebriometer four times at 2 hour intervals. Control flies which are preexposed to a heat shock show a 46 +/- 4% increase in mean elution time (MET) when exposed to ethanol in an inebriometer 4 hours later. This heat-ethanol cross tolerance is substantially reduced in hangAE10 flies (only a 26 +/- 4% increase in MET is seen). Mutant flies show a decreased lifespan under control conditions and show increased sensitivity to paraquat compared to controls. The overall brain structure of mutant adults appears to be normal, even in old flies.
Molecular genetic and phenotypic characterizations suggest that hangAE10 mutants are impaired in specific cellular stress responses.
hangAE10 has chemical sensitive | adult stage phenotype, non-enhanceable by Pde4Δ143
hangAE10 has chemical sensitive | adult stage phenotype, suppressible by Pde4Δ143
hangAE10 is a suppressor of chemical sensitive | adult stage phenotype of Pde4Δ143
The reduced heat-induced ethanol (EtOH) resistance characteristic for hangAE10 mutant adults is not exacerbated further by combination with dncΔ143 which on its own also lead to a decrease in the heat > ethanol cross-tolerance.
hangAE10;dncΔ143 double mutant adult flies display normal ethanol tolerance development upon re-exposition to EtOH, unlike each of the single mutants that show significantly reduced tolerance buildout.
hangAE10 is rescued by Scer\GAL4Pde4.RA/hangUAS.cSa
hangAE10 is rescued by Scer\GAL4NP6510/hangUAS.cSa
hangAE10 is rescued by Scer\GAL4Appl.G1a/hangUAS.cSa
The reduced ability of hangAE10 mutant adults to develop tolerance to ethanol upon re-exposition is rescued by expression of hangScer\UAS.cSa under the control of either Scer\GAL4dnc.RA or Scer\GAL4NP6510 together with tub-Gal80[ts] to limit the expression to a short period before the inebriation test (temporally unrestricted expression of hangScer\UAS.cSa in the mutant background using either of the two drivers is lethal).
Precise excision of the P{PZ} element reverts the mutant phenotype.