Nf1P1/Nf1P2 transheterozygotes present a fully penetrant lack of circadian rhythmicity and a severe decrease in sleep time; Nf1P1 heterozygotes show a minor decrease in rhythmicity.
Nf1P1 mutant adults on average display significant increase activity at night and loss of sleep both during the day and at night. The increase in activity is largely due to relatively sparse but large bursts of activity that are more frequent in Nf1P1 mutants than wild-type. This large bursts of activity represent grooming behavior rather than locomotion.
Nf1P1 mutant adults display significant increase in grooming frequency as well as average duration of grooming behavior bouts compared to wild-type both immediately after introduction into the experimental arena and after 15 min period of acclimatization. The overall increase in grooming is due to elevated head/eye grooming initially but after acclimatization abdomen and hind legs grooming is also increased compared to controls.
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.
Nf1P1 mutants exhibit a 60-73% reduction in life span, relative to controls. Nf1P1/Nf1P2 transheterozygotes exhibit a life span similar to Nf1P2 flies, i.e., they exhibit a 24-40% reduction in life span.
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.
The ADP-stimulated respiration rate and the derived ATP synthesis rate are reduced by approximately 50% in Nf1P1 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 37% 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.
Mutant flies show no rhythmicity in locomotor activity when kept under constant darkness conditions. Average locomotor activity is normal under these conditions. 22.73% of Nf1P1/Df(3R)Espl3 flies show weak 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. Nf1P1 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 the PACAP38-like 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. In homozygotes 25% ommatidia have one or more extra photoreceptor cells. Homozygotes exhibit reduced escape response due to defects at the larval neuromuscular junction.