Imprecise excision of P{EPgy2}5-HT1AEY09988 results in deletion of more than 5kb of genomic sequence including the 3' coding region of 5-HT1A. The last two exons, which encode the sixth and seventh transmembrane domains, the C-terminal end, and a part of the third intracellular loop are deleted.
Similar to wild type, 5-HT1AΔ5kb/5-HT1AGal4 larvae are sensitive to 100μM metitepine and show decreased feeding rates when fed with this drug.
5-HT1AΔ5kb mutant flies display reduced lifespans in starvation conditions. This lifespan is reduced further upon feeding with a 5-HT1A agonist (WAY100635).
5-HT1AΔ5kb mutant flies display a decreased tolerance to heat. Likewise, these flies require increased time to recover from cold coma induced by exposure to 0[o]C for 4 hours.
Heterozygous 5-HT1AΔ5kb mutant flies display a significant reduction of lipid levels compared to control flies at 12 and 24 hours of starvation.
Heterozygous 5-HT1AΔ5kb mutant adult flies (4-6 days old) do not exhibit a significant difference in weight compared to controls.
5-HT1AΔ5kb flies exhibit significantly reduced sleep and sleep bout length as compared to control flies.
The circadian profile of activity and sleep in 5-HT1AΔ5kb mutants indicates that the onset and offset of activity, as well as the distribution of sleep are similar in the mutant as in control flies. However, 5-HT1AΔ5kb mutants exhibit significantly reduced total sleep and sleep bout length, as well as an increased number of sleep bouts, indicating that sleep is both reduced and fragmented. Significant changes are only found for night-time sleep in females, since they exhibit limited and poorly consolidated daytime sleep. Male 5-HT1AΔ5kb mutants exhibit reduced overall sleep relative to their controls, evident both during the day and night.
5-HT1AΔ5kb mutants, transferred from light-dark cycles to constant darkness conditions exhibit a reduction in the total sleep and sleep bout length, while sleep bout number increases. 5-HT1AΔ5kb mutants show significantly larger changes in these parameters in response to the absence of light-dark cycles, suggesting that mechanisms for maintaining sleep stability are impaired in these flies.
5-HT1AΔ5kb mutants deprived of sleep by subjection to mechanical sleep deprivation for 6 hours in the latter half of the night exhibit significantly reduced sleep rebound compared to controls.
5-HT1AΔ5kb mutants do not have visible defects in body and brain development or in locomotion. In circadian behavioral assays, 5-HT1AΔ5kb mutant flies exhibit normal free-running rhythms, although the strength of the rhythm is reduced.
5-HT1AΔ5kb mutants do not exhibit increased photosensitivity (as measured by light-induced phase shifts in the late night).
5-HT1AΔ5kb has abnormal behavior phenotype, non-suppressible by Scer\GAL4Mef2.247.Switch/5-HT1BUAS.cYa
Expression of 5-HT1BScer\UAS.cYa, under the control of Scer\GAL4Mef2.247.Switch does not rescue the 5-HT1AΔ5kb sleep phenotype.
Expression of 5-HT1BIR.Scer\UAS, under the control of RU486-inducible Scer\GAL4Mef2.247.Switch in a 5-HT1AΔ5kb heterozygous background does not produce any baseline sleep phenotype.
5-HT1AΔ5kb is rescued by Scer\GAL4elav-C155/5-HT1AUAS.cRa
Expression of 5-HT1AScer\UAS.cRa pan-neuronally, under the control of Scer\GAL4elav-C155 restores sleep levels and consolidation in 5-HT1AΔ5kb mutants, with total sleep and night-time sleep bout length increasing while bout number decreases.
Total daily sleep and night-time sleep bout length are restored to wild-type levels in RU486-treated 5-HT1AScer\UAS.cRa mutants, driven with Scer\GAL4Mef2.247.Switch (activated by RU486).
