Dmel\P{lacW}Nf1^P2 Insertion

General Information
Symbol	Dmel\P{lacW}Nf1^P2	Species	D. melanogaster
Name		FlyBase ID	FBti0004365
Feature type	transposable_element_insertion_site
Description
Inserted element	P{lacW}	Expression data
Affected gene(s)	Nf1	Viability / fertility	fertile, viable
Causes allele(s)	Nf1^P2	Stock availability	none publicly available
LINE ID
Genomic Location
Chromosomal location	3R ( 96F9 )	Sequence location
Member of Large Scale Dataset(s)
Dataset
Recent Updates
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FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Detailed Mapping Data
Chromosome (arm)
Sequence Location
Orientation
Cytological location (computed by FlyBase)	96F9 ( near gene of known cytology )
Cytological location (reported)
Comments concerning location
Sequence Data
Flanking sequence
Inserted Element
Construct	P{lacW}
Location-dependent role	lacZ enhancer trap (Bier et al., 1989)
Size	10.691Kb
Associated alleles	Ecol\lacZ^P\T.W w^+mC
Molecular map
Affected Gene(s)
Insertion may affect gene	Nf1 (The et al., 1997, Tong et al., 2007, Buchanan and Davis, 2010)
Alleles and Phenotypes
Causes alleles	Nf1^P2 (The et al., 1997, Guo et al., 1997, Tong et al., 2007, Buchanan and Davis, 2010)

Lethality References viable (The et al., 1997, Guo et al., 1997)
Sterility References fertile (The et al., 1997)
Phenotype Manifest In
	eye photoreceptor cell (The et al., 1997) pupa (Walker et al., 2006) surface associated glial cell (Yager et al., 2001)
Detailed Description
Statement Reference Nf1[P2] males and females are significantly smaller than controls. In training trial assays, where flies are repeatedly trained with odor avoidance assays, Nf1[P2] flies perform poorly even after 15 trials, at which point their performance is not significantly different to controls. Normalisation of Nf1[P2] performance (to take into account memory decay) required training with seven trials while the control is trained with three trials. Memory of Nf1[P2] mutants, when tested at two subsequent time points, is indistinguishable from controls. (Buchanan and Davis, 2010) The paraquat sensitivity of Nf1[P2] mutant flies is eliminated in Nf1[hs.PT]/+; Nf1[P2] mutants. Addition of Nf1[hs.PT] restores the ADP-stimulated respiration rate and the derived ATP synthesis rate in Nf1[P2] mutants to wild-type levels. Mitochondrial aconitase activity is restored by expression of Nf1[hs.PT] in a Nf1[P2] mutant background. Elevated superoxide levels in Nf1[P2] mutant flies are reduced to wild-type levels by the introduction of Nf1[hs.PT]. (Tong et al., 2007) The presence of the heat shock-inducible and constitutively active Mmus\Pkaca[hs.PJ] suppresses the reduction in life span and reduced tolerance to heat stress seen in Nf1[P2] mutants. Expression of Mmus\Pkaca[hs.PJ] in a Nf1[P2] mutant background greatly increases the resistance to paraquat-induced oxidative stress. Expression of constitutively active Mmus\Pkaca[hs.PJ] increases mitochondrial aconitase activity by over 90%, even in the absence of Nf1 (in a Nf1[P2] mutant background). Addition of Mmus\Pkaca[hs.PJ] restores the ADP-stimulated respiration rate and the derived ATP synthesis rate in Nf1[P2] mutants to wild-type levels. (Tong et al., 2007) Nf1[P2] mutants exhibit a 24-40% reduction in life span, relative to controls.Nf1[P1]/Nf1[P2] transheterozygotes exhibit a life span similar to Nf1[P2] flies. Nf1[P2] mutants exhibit a drop in physical fitness compared to controls. Nf1[P2] and Nf1[P2]/Nf1[P1] 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. Nf1[P2] mutant flies are as resistant to desiccation as controls. Nf1[P2] mutant flies are significantly more sensitive to paraquat-induced oxidative stress, compared to controls. Mitochondrial aconitase activities in 30-day old Nf1[P2] 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 Nf1[P2] flies, whereas the non-ADP-stimulated respiration is unaffected. Nf1[P1]/Nf1[P2] 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 Nf1[P1]/Nf1[P2] flies by approximately 50%, indicating that increased superoxide anion production is the cause of the reduced life span found in Nf1[P1]/Nf1[P2] mutants. These drugs also enhance the recovery rate of locomotive performance of Nf1[P1]/Nf1[P2] mutants after heat stress. (Tong et al., 2007) rut[1]; Nf1[P2] mutants do not exhibit shorter life spans compared to rut[1] single mutants. The lifespan of dnc[1]; Nf1[P2] flies is as wild-type, indicating that the reduced life span found in Nf1[P2] mutants is the product of reduced cAMP levels. These flies also show suppression of the reduced tolerance to heat stress seen in Nf1[P2]. rut[1]; Nf1[P2] 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. rut[1]; Nf1[P2] mutant flies are significantly more sensitive to paraquat-induced oxidative stress, compared to controls. Mitochondrial aconitase activities in 30-day old rut[1]; Nf1[P2] flies are reduced by 76% compared to controls (and 36% in Nf1[P2]). The ADP-stimulated respiration rate and the derived ATP synthesis rate are reduced by approximately 50% in rut[1]; Nf1[P2] flies, whereas the non-ADP-stimulated respiration is unaffected. Superoxide levels are increased in rut[1]; Nf1[P2] flies compared to controls. (Tong et al., 2007) 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] } (Hannan et al., 2006) 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 Nf1^P1/Df(3R)Espl3 flies show rhythmic locomotor activity under constant darkness conditions. (Williams et al., 2001) Significant 25-hour locomotor activity rhythms are detected in only 51% of Nf1^P1 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. (Williams et al., 2001) The addition of ine¹ or poe¹ enhances the Nf1^P2 perineurial glial thickness phenotype. The addition of eag¹ only moderately enhances the ine¹ perineurial glial thickness phenotype. (Yager et al., 2001) The learning scores of rut¹; Nf1^P2 double mutant flies are similar to that of either single mutant. (Guo et al., 2000) The short-term memory defect of Nf1^P2 flies is completely rescued by heat shock induced expression of Mmus\Pkaca^hs.PJ. Mmus\Pkaca^hs.PJ partially rescues the learning defect of Nf1^P2 when the flies are raised at room temperature, and completely rescues Nf1^P2 when it is expressed using heat shock (37^oC, 30 minutes). (Guo et al., 2000) 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. Nf1^P2 flies show a short-term memory defect (3 and 8 hour retention). (Guo et al., 2000) 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. (Guo et al., 1997) Phenotype is rescued by heat induced expression of Nf1^hs.PT. (Guo et al., 1997) 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. (The et al., 1997) The growth defect can be rescued by heat induced expression of Nf1^hs.PT. (The et al., 1997) 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. (Zhong, 1997)
Expression Data
Reporter Expression

Additional Information
Statement Reference

Marker for
Reflects expression of
Reporter construct used in assay
External Images
FlyView (LinkOut)
Data on Genetic Line
Line ID
Origin as a multiple insertion line
Progenitor(s) within the Genome
Transposed descendant of	P{lacW}K33
Related Aberration or Balancer
Aberration
Balancer
Stocks ( 0 )

Linkouts
Synonyms & Secondary IDs
Reported As
Symbol Synonym	nf1^P2 (Buchanan and Davis, 2010) Nf1^P2 (Tong et al., 2007) P{lacW}Nf1^P2 (The et al., 1997, FlyBase, 1992-)
Secondary FlyBase IDs

References ( 13 )
Research paper	Buchanan and Davis, 2010, J. Neurosci. 30(30): 10135--10143 A distinct set of Drosophila brain neurons required for neurofibromatosis type 1-dependent learning and memory. [FBrf0211411] Tong et al., 2007, Nat. Genet. 39(4): 476--485 Life extension through neurofibromin mitochondrial regulation and antioxidant therapy for neurofibromatosis-1 in Drosophila melanogaster. [FBrf0200172] Hannan et al., 2006, Hum. Mol. Genet. 15(7): 1087--1098 Effect of neurofibromatosis type I mutations on a novel pathway for adenylyl cyclase activation requiring neurofibromin and Ras. [FBrf0190827] Walker et al., 2006, Genes Dev. 20(23): 3311--3323 Reduced growth of Drosophila neurofibromatosis 1 mutants reflects a non-cell-autonomous requirement for GTPase-Activating Protein activity in larval neurons. [FBrf0193208] Williams et al., 2001, Science 293(5538): 2251--2256 A circadian output in Drosophila mediated by Neurofibromatosis-1 and Ras/MAPK. [FBrf0138535] Yager et al., 2001, Proc. Natl. Acad. Sci. U.S.A. 98(18): 10445--10450 Control of Drosophila perineurial glial growth by interacting neurotransmitter-mediated signaling pathways. [FBrf0138519] Guo et al., 2000, Nature 403(6772): 895--898 A neurofibromatosis-1-regulated pathway is required for learning in Drosophila. [FBrf0125468] Guo et al., 1997, Science 276(5313): 795--798 Requirement of Drosophila NF1 for activation of adenylyl cyclase by PACAP38-like neuropeptides. [FBrf0093486] The et al., 1997, Science 276(5313): 791--794 Rescue of a Drosophila NF1 mutant phenotype by protein kinase A. [FBrf0093751] Bier et al., 1989, Genes Dev. 3: 1273--1287 Searching for pattern and mutation in the Drosophila genome with a P-lacZ vector. [FBrf0049800]
Supplementary material	Williams et al., 2001, Science 293(5538): A circadian output in Drosophila mediated by Neurofibromatosis-1 and Ras/MAPK. [FBrf0141792]
Abstract	Zhong, 1997, A. Rep. Cold Spring Harbor Lab. 1996: 178--181 Neural basis of learning and memory in Drosophila. [FBrf0098129]
FlyBase analysis	FlyBase, 1992-, FlyBase curation. FlyBase curation. [FBrf0105495]

Dmel\P{lacW}Nf1P2 Insertion

Dmel\P{lacW}Nf1^P2 Insertion