The expression of Hsap\HTTQ128.UAS under the control of Scer\GAL4P2.4.Pdf severely impairs circadian behavior, and leads to a severe decrease in the number of sLNv nurons in 10-days old adults.
Most of the adult flies expressing Hsap\HTTQ128.Scer\UAS under the control of Scer\GAL4P2.4.Pdf show arrhythmic locomotor activity from the first day in constant darkness (DD) as well as poor consolidation of daily activity, whereas all control flies are rhythmic. The Hsap\HTTQ128.Scer\UAS-expressing flies have significantly fewer s-LNv somas that label positive for either Pdf or per, in contrast the number of Pdf-positive l-LNv neurons is comparable to controls but only about half of these is also positive for per. However, there is no significant difference in the number of Pdf+ s-LNv neurons between Hsap\HTTQ128.Scer\UAS-expressing flies that are (weakly) rhythmic and those completely arrhythmic and both these groups show Pdf immunoreactivity in the dorsal projections of s-LNv neurons. The Pdf levels in these dorsal projections oscillate after transfer to DD and while the peak coincides with the timing observed in control flies but the rise and fall of Pdf in Hsap\HTTQ128.Scer\UAS flies occurs earlier than in controls. per protein levels in the somas of l-LNv neurons do not oscillate and are very low relative to flies expressing Hsap\HTTQ0.Scer\UAS, whereas they oscillate with similar phase and overall intensity in other (Pdf-negative) neuronal groups (LNd, DN1, DN2 or the 5th s-LNv).
Adult flies expressing Hsap\HTTQ128.Scer\UAS continue to show anticipation of the dark-light transition even under low light intensity LD (light-dark) cycles and, like controls, show a clear oscillation in Pdf levels in s-LNv dorsal projections. On average, fewer per+ s-LNv somas are found in Hsap\HTTQ128.Scer\UAS expressing flies compared to Hsap\HTTQ0.Scer\UAS flies. The number of Pdf and per positive l-LNv somas are comparable between the two genotypes and in these neurons the per protein shows clear oscillation under LD although the amplitude is dampened in Hsap\HTTQ128.Scer\UAS flies compared to Hsap\HTTQ0.Scer\UAS.
Hsap\HTTQ128.Scer\UAS;Scer\GAL4P2.4.Pdf flies raised and maintained in constant light (LL) show a progressive loss of Pdf from s-LNv neurons' dorsal projections, flies maintained in LL, transferred to LD and then DD (the LL-LD regimen) show no Pdf+ s-LNv somas at age 23 and 28 days, not even after experiencing 5 days in LD. The numbers of Pdf+ l-LNv somas is comparable between regimens. Both LL-LD and LD-LD flies Scer\GAL4P2.4.Pdf>Hsap\HTTQ128.Scer\UAS flies exhibit activity profiles similar to their in-regimen controls and also show no differences in their morning and evening anticipation behavior relative to controls and across regimens.
Expression of Hsap\HTTQ128.Scer\UAS under the control of Scer\GAL4elav.PLu results in time-dependent neurodegeneration. Newly eclosed flies have the normal complement of seven visible rhabdomeres per ommatidium, but this is reduced by day 10 post-eclosion. Treatment with meclizine partially rescues this phenotype.
Expression of Hsap\HTTQ128.Scer\UAS under the control of an unknown Gal4 driver severely reduces adult survival rates.
One day old flies expressing Hsap\HTTQ128.Scer\UAS under the control of Scer\GAL4GMR.PF show photoreceptor degeneration, resulting in loss of rhabdomeres in each ommatidium. This photoreceptor degeneration is suppressed upon treatment with the HSF1-activating compound 17-AAG. Treatment with GA and RA modestly increases the number of rhabdomeres, as does the histone deacetylase inhibitor SB.
When Hsap\HDQ128.Scer\UAS is driven by Scer\GAL4GMR.PF a rough eye phenotype is seen. A loss of pigmentation is seen in the eye as well as abnormal bristle pattern and photoreceptor degeneration. A neurophysiological phenotype is also seen; mutant animals show reduced photoreceptor depolarisation and complete abolishment of synaptic transmission in response to light. Cytoplasmic Hsap\HD aggregates are seen in neurons, aggregates are transported in larval motor axons and accumulate in presynaptic neuromuscular junction terminals When Hsap\HDQ128.Scer\UAS is driven by Scer\GAL4elav-C155, larvae show a significant reduction in locomotor speed of about 25% from 1.23 mm/s to 0.92 mm/s. In adults expression of Hsap\HDQ128.Scer\UAS by Scer\GAL4elav-C155 cause adult lethality. When driven by Scer\GAL4elav.PLu adults are fully viable, however, several days after eclosion, mutant adults begin to exhibit uncoordinated movement and abnormal grooming behaviour. These behaviours worsen with age, resulting in premature death. When Hsap\HDQ128.Scer\UAS is driven by Scer\GAL4elav-C155, Hsap\HD cytoplasmic aggregates are seen in neurons. When driven by Scer\GAL4αTub84B.PL cytoplasmic aggregates are seen in both neuronal and non-neuronal tissues. No nuclear aggregates are seen.