Nf1P1/Nf1P2 transheterozygotes present a fully penetrant lack of circadian rhythmicity and a severe decrease in sleep time
Nf1P1/Nf1P2 male flies sleep significantly less than wild type flies, whereas females do not show consistent differences; sleep is also fragmented, as males have significantly reduced bout duration and increased bout number and females have significantly increased bout number. Both male and female Nf1P1/Nf1P2 flies exhibit nocturnal hyperactivity (resulting in an increase in daytime sleep and a decrease in nighttime sleep), and are arrhythmic in dark conditions. Nf1P2/Nf1c00617 male or female flies sleep significantly less than wild type.
Nf1P2 males and females are significantly smaller than controls.
In training trial assays, where flies are repeatedly trained with odor avoidance assays, Nf1P2 flies perform poorly even after 15 trials, at which point their performance is not significantly different to controls. Normalisation of Nf1P2 performance (to take into account memory decay) required training with seven trials while the control is trained with three trials. Memory of Nf1P2 mutants, when tested at two subsequent time points, is indistinguishable from controls.
Nf1P2 mutants exhibit a 24-40% reduction in life span, relative to controls.Nf1P1/Nf1P2 transheterozygotes exhibit a life span similar to Nf1P2 flies.
Nf1P2 mutants exhibit a drop in physical fitness compared to controls. Nf1P2 and Nf1P2/Nf1P1 flies take over 100 minutes to recover from a 20 minute 37[o]C heat stress, as shown by a locomotive index generated with a climbing assay.
Nf1P2 mutant flies are as resistant to desiccation as controls.
Nf1P2 mutant flies are significantly more sensitive to paraquat-induced oxidative stress, compared to controls.
Mitochondrial aconitase activities in 30-day old Nf1P2 flies are reduced by 36% compared to controls.
The ADP-stimulated respiration rate and the derived ATP synthesis rate are reduced by approximately 50% in Nf1P2 flies, whereas the non-ADP-stimulated respiration is unaffected.
Nf1P1/Nf1P2 mitochondria generate more superoxide than control mitochondria.
Exposure to Mn(III)tetrakis(4-benzoic acid) porphin and tetrakis(1,3-diethyl imidazolium-2-yl) meso-substituted manganoporphyrin (MnTDEIP) increases the survivorship of Nf1P1/Nf1P2 flies by approximately 50%, indicating that increased superoxide anion production is the cause of the reduced life span found in Nf1P1/Nf1P2 mutants. These drugs also enhance the recovery rate of locomotive performance of Nf1P1/Nf1P2 mutants after heat stress.
Significant 25-hour locomotor activity rhythms are detected in only 51% of Nf1P1 flies in LD (12 hour light:12 hour dark) conditions. Flies that do show significant rhythms do not show a consistent activity peak or the anticipatory behaviour that normally accompanies the light:dark transitions.
Only 10.53% of mutant flies show weak rhythmicity in locomotor activity when kept under constant darkness conditions. Average locomotor activity is normal under these conditions. 6.67% of Nf1P1/Df(3R)Espl3 flies show rhythmic locomotor activity under constant darkness conditions.
Flies show a significant decrease in olfactory learning performance compared to controls. Olfactory avoidance and electric-shock reactivity are similar in mutant and control flies. Mutants have a smaller body size than wild-type flies. Nf1P2 flies show a short-term memory defect (3 and 8 hour retention).
Modulation of voltage gated K+ currents induced by the neuropeptide pituitary adenylyl cyclase-activating polypeptide (PACAP38) is eliminated. Application of cAMP analogs or forskolin is sufficient to restore PACAP38 enhancement of K+ currents.
Homozygotes are 20-25% smaller than wild type during postembryonic stages. Clones in the wings demonstrates the reduced size of wing epidermal cells reflects a cell-autonomous defect, clones in the eye show a reduced number of ommatidia of normal size and structure. Heterozygous loss of Sos or Ras85D has no effect on size of Nf1 mutant pupae, nor does expression of an activated phl mutation. In homozygotes 25% ommatidia have one or more extra photoreceptor cells. Homozygotes exhibit reduced escape response due to defects at the larval neuromuscular junction.
Eliminates the activation of the rut-encoded adenylyl cyclase eliminating the pituitary-adenylyl-cyclase-activating polypeptide (PACAP38) response. The defect can be fully restored by supplying drugs that stimulate the cAMP pathway prior to perfusion of PACAP38. Associative learning is defective.