Expression of
Hsap\APPAβ42.Scer\UAS.cUa under the control of
Scer\GAL4GMR.PU results in a severe reduction in the size of the adult eye as compared to wild type, and the eye has a glazed appearance due to the fusion of lenses; third instar eye discs from these mutants show a significant increase in cell death and defective axonal targeting of the retinal neurons, as compared to controls.
Expression of
Hsap\APPAβ42.Scer\UAS.cUa under the control of
Scer\GAL4elav-C155 results in age-progressive neurodegeneration (vacuole lesions in the brain of aged adult flies) and earlier and more severe age-related decline in climbing ability.
Flies expressing
Hsap\APPAβ42.Scer\UAS.cUa in the central nervous system under the control of
Scer\GAL4elav.PU display disease phenotypes, including reduced longevity and a gradual decline of locomotive ability. Feeding flies with compound D737 (C[[25]]H[[20]]N[[2O]]) increases longevity of the flies compared with controls. Similarly, feeding flies with D737 analogues D744, D830, D979 and D742 also results in improved longevity. The most effective of these compounds (D744) produces a life span curve for the transgenic flies that is fairly close to that of wild-type. Compound D737 and all four analogues also ameliorate the climbing defects in the transgenic flies.
Expression of
Hsap\APPAβ42.Scer\UAS.cUa in the wing, under the control of
Scer\GAL4Bx-MS1096, generates ectopic and defective wing vein formation. Addition of KSOP1009 to the food media suppresses defective wing vein formation. Addition of PD98059 to the food media suppresses defective wing vein formation.
Expression of
Hsap\APPAβ42.Scer\UAS.cUa under the control of
Scer\GAL4elav-C155 decreases climbing ability, compared to wild-type flies. Addition of 50υM PD98059 to the food media for these flies restores climbing ability. Addition of 5υg/mL KSOP1009 also restores climbing ability in these flies.
Pan-neuronal expression of
Hsap\APPAβ42.Scer\UAS.cUa, under the control of
Scer\GAL4elav-C155, increases the number of glial cells in the larval brain. Addition of 5υg/mL KSOP1009 to fly media almost completely restores the number of glial cells in mutant larval brains to control levels. Addition of PD98059 does not affect glial cell proliferation.
Expression of
Hsap\APPAβ42.Scer\UAS.cUa under the control of
Scer\GAL4GMR.PU results in reduced eyes with a glazed surface. Mutant eye imaginal discs show an almost three-fold increase in TUNEL-positive cells compared to controls. Aberrant axonal targeting from the retina to the brain is seen, with the retinal axons failing to innervate the medulla and lamina and ending abruptly.
Defects can be seen in the third larval instar eye disc in animals expressing
Hsap\APPAβ42.Scer\UAS.cUa under the control of
Scer\GAL4GMR.PU. Improper spacing of the differentiating photoreceptors and mild fusion of the ommatidial clusters is seen. At the prepupal stage, mild to stronger fusion of the ommatidial clusters is seen resulting in clumps of photoreceptors and loss of photoreceptors in the ommatidium. The phenotype becomes progressively more severe during the pupal stage, with multiple fusions of ommatidia and holes in the retina where ommatidial clusters have been extruded. The adult eye is severely diminished in size and shows ommatidial fusion, which in severe cases leads to a glazed appearance. The retina of the adult eye is very thin, has poorly differentiated photoreceptors and is vacuolated, and the overlying lenses are fused with it.
TUNEL positive cells begin to appear as early as the late third larval instar in the eye discs of animals expressing
Hsap\APPAβ42.Scer\UAS.cUa under the control of
Scer\GAL4GMR.PU.
