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General Information
Symbol
Dmel\Nf1P2
Species
D. melanogaster
Name
FlyBase ID
FBal0061707
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Nature of the Allele
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Associated Sequence Data
DNA sequence
Protein sequence
 
 
Cytology
Nature of the lesion
Statement
Reference

P{lacW} insertion in the first intron.

Insertion components
P{lacW}Nf1P2
Product class / Tool use(s)
Encoded product / tool
Expression Data
Reporter Expression
Additional Information
Statement
Reference
 
Marker for
Reflects expression of
Reporter construct used in assay
Human Disease Associations
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 1 )
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 1 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

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.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement
Reference

Nf1P2 has locomotor rhythm defective | heat sensitive phenotype, enhanceable by Mmus\Prkacahs.PJ

Nf1P2 has oxidative stress response defective | heat sensitive phenotype, enhanceable by Mmus\Prkacahs.PJ

NOT Enhanced by
Statement
Reference

Nf1P2/Nf1P1 has sleep defective phenotype, non-enhanceable by SIFa3/SIFa2

Nf1P2/Nf1P1 has sleep defective phenotype, non-enhanceable by SIFa1/SIFa[+]

Nf1P2/Nf1P1 has sleep defective phenotype, non-enhanceable by SIFa[+]/SIFa2

Nf1P2/Nf1P1 has sleep defective phenotype, non-enhanceable by SIFa3/SIFa[+]

Suppressed by
NOT suppressed by
Statement
Reference

Nf1P2/Nf1P1 has circadian rhythm defective | adult stage phenotype, non-suppressible by Pdfr[+]/Pdfr3369

Nf1P2/Nf1P1 has circadian rhythm defective | adult stage phenotype, non-suppressible by Pdfr[+]/Pdfr5304

Nf1P2/Nf1P1 has sleep defective phenotype, non-suppressible by SIFa1/SIFa[+]

Nf1P2/Nf1P1 has sleep defective phenotype, non-suppressible by SIFa[+]/SIFa2

Nf1P2/Nf1P1 has sleep defective phenotype, non-suppressible by SIFa3/SIFa[+]

Nf1P2/Nf1P1 has sleep defective phenotype, non-suppressible by SIFa3/SIFa2

Nf1P2 has locomotor rhythm defective phenotype, non-suppressible by dnc1

Nf1P2 has locomotor rhythm defective phenotype, non-suppressible by dncML

Enhancer of
Statement
Reference

Nf1P2/Nf1P1 is an enhancer of sleep defective phenotype of SIFa3/SIFa2

Suppressor of
Statement
Reference
Other
Statement
Reference
Phenotype Manifest In
Enhanced by
Statement
Reference
Enhancer of
Statement
Reference
Additional Comments
Genetic Interactions
Statement
Reference

Nf1P1 heterozygosity suppresses the shorter circadian period of Pdfr5304 and Pdfr3369 hemizygotes and partially suppresses the circadian arrhythmicity of Pdfr3369 hemizygotes, but not of Pdfr5304 hemizygotes.

Nf1P1/Nf1P2 mutations suppress (to different degrees) the long sleep phenotype seen in Alkts/Alk1 males and females at different temperatures (18, 25 or 29[o]C). In male flies, Alkts/Alk1;Nf1P1/Nf1P2 double mutants even sleep significantly less than wild type flies.

Alkts/Alk1 does not suppress arrhythmicity (in dark conditions) in Nf1P1/Nf1P2 flies.

rut1; Nf1P2 mutants do not exhibit shorter life spans compared to rut1 single mutants.

The lifespan of dnc1; Nf1P2 flies is as wild-type, indicating that the reduced life span found in Nf1P2 mutants is the product of reduced cAMP levels. These flies also show suppression of the reduced tolerance to heat stress seen in Nf1P2.

rut1; Nf1P2 flies exhibit a delay in recovery time from a 20 minute 37[o]C heat stress, as shown by a locomotive index generated with a climbing assay.

rut1; Nf1P2 mutant flies are significantly more sensitive to paraquat-induced oxidative stress, compared to controls.

Mitochondrial aconitase activities in 30-day old rut1; Nf1P2 flies are reduced by 76% compared to controls (and 36% in Nf1P2).

The ADP-stimulated respiration rate and the derived ATP synthesis rate are reduced by approximately 50% in rut1; Nf1P2 flies, whereas the non-ADP-stimulated respiration is unaffected.

Superoxide levels are increased in rut1; Nf1P2 flies compared to controls.

The addition of ine1 or poe1 enhances the Nf1P2 perineurial glial thickness phenotype. The addition of eag1 only moderately enhances the ine1 perineurial glial thickness phenotype.

The learning scores of rut1; Nf1P2 double mutant flies are similar to that of either single mutant.

Xenogenetic Interactions
Statement
Reference

The presence of the heat shock-inducible and constitutively active Mmus\Pkacahs.PJ suppresses the reduction in life span and reduced tolerance to heat stress seen in Nf1P2 mutants.

Expression of Mmus\Pkacahs.PJ in a Nf1P2 mutant background greatly increases the resistance to paraquat-induced oxidative stress.

Expression of constitutively active Mmus\Pkacahs.PJ increases mitochondrial aconitase activity by over 90%, even in the absence of Nf1 (in a Nf1P2 mutant background).

Addition of Mmus\Pkacahs.PJ restores the ADP-stimulated respiration rate and the derived ATP synthesis rate in Nf1P2 mutants to wild-type levels.

small body | pupal stage, suppressible { Hsap\NF1[Scer\UAS.cHa], Scer\GAL4[e22c] }

small body | pupal stage, suppressible { Hsap\NF1[L847P.Scer\UAS], Scer\GAL4[e22c] }

small body | pupal stage, suppressible { Hsap\NF1[R1276P.Scer\UAS], Scer\GAL4[e22c] }

small body | pupal stage, suppressible { Hsap\NF1[R1391S.Scer\UAS], Scer\GAL4[e22c] }

small body | pupal stage, suppressible { Hsap\NF1[K1423E.Scer\UAS], Scer\GAL4[e22c] }

small body | pupal stage, non-suppressible { Hsap\NF1[GRD1.Scer\UAS], Scer\GAL4[e22c] }

small body | pupal stage, non-suppressible { Hsap\NF1[GRD2.Scer\UAS], Scer\GAL4[e22c] }

small body | pupal stage, non-suppressible { Hsap\NF1[Nterm.Scer\UAS], Scer\GAL4[e22c] }

small body | pupal stage, suppressible { Hsap\NF1[ΔGRD2.Scer\UAS], Scer\GAL4[e22c] }

small body | pupal stage, suppressible { Hsap\NF1[Cterm.Scer\UAS], Scer\GAL4[e22c] }

The short-term memory defect of Nf1P2 flies is completely rescued by heat shock induced expression of Mmus\Pkacahs.PJ. Mmus\Pkacahs.PJ partially rescues the learning defect of Nf1P2 when the flies are raised at room temperature, and completely rescues Nf1P2 when it is expressed using heat shock (37oC, 30 minutes).

Complementation and Rescue Data
Partially rescued by
Comments

Expression of Nf1Scer\UAS.cdNa driven by Scer\GAL4nSyb.PS rescues the decreases in total sleep seen in Nf1P1/Nf1P2 male and female flies, even significantly increasing total sleep beyond wild type amounts.

The paraquat sensitivity of Nf1P2 mutant flies is eliminated in Nf1hs.PT/+; Nf1P2 mutants.

Addition of Nf1hs.PT restores the ADP-stimulated respiration rate and the derived ATP synthesis rate in Nf1P2 mutants to wild-type levels.

Mitochondrial aconitase activity is restored by expression of Nf1hs.PT in a Nf1P2 mutant background.

Elevated superoxide levels in Nf1P2 mutant flies are reduced to wild-type levels by the introduction of Nf1hs.PT.

Phenotype is rescued by heat induced expression of Nf1hs.PT.

The growth defect can be rescued by heat induced expression of Nf1hs.PT.

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Mutant
Wild-type
Stocks (0)
Notes on Origin
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External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (3)
References (17)