FlyBase Allele Report: Hsap\APP[Arctic.Aβ42.UAS.cJa.Tag:SS(nec)]

General Information

Symbol

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}

Species

H. sapiens

Name

FlyBase ID

FBal0294067

Feature type

allele

Associated gene

Hsap\APP

Associated Insertion(s)

Carried in Construct

M{UAS-ArcticAβ42.J}

Also Known As

UAS-Aβ₄₂arc, Aβ-Arc

Key Links

Transgenic product class

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

Mutagen

in vitro construct

(Jahn et al., 2011)

Progenitor genotype

Carried in construct

M{UAS-ArcticAβ42.J}

Cytology

Description

UAS regulatory sequences drive expression of an arctic variant (E22G) Aβ1-42 peptide.

(Jahn et al., 2011)

Allele components

Component

Use(s)

Regulatory region(s)

UAS

binary expression system - regulatory region

Encoded product / tool

Hsap\APP

Tagged with

Tag:SS(nec)

signal sequence

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

Variant Molecular Consequences

Associated Sequence Data

DDBJ / EMBL / GenBank

DNA sequence

Protein sequence

UniProtKB/Swiss-Prot

UniProtKB/TrEMBL

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

model of Alzheimer's disease

CEA

(Chen et al., 2014, Favrin et al., 2013, Kruppa et al., 2013, Jahn et al., 2011)

model of Alzheimer's disease 1

CEA

(Wilson et al., 2024, Yu et al., 2024, Younan et al., 2018, Ott et al., 2016)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of Alzheimer's disease

is ameliorated by PGRP-SC1b^GD5490

(Favrin et al., 2013)

is ameliorated by CG14715^KK104150

(Favrin et al., 2013)

is ameliorated by CG14715^GD4788

(Favrin et al., 2013)

is ameliorated by Sod3^GD4801

(Favrin et al., 2013)

is ameliorated by CG14715^G6908

(Favrin et al., 2013)

model of Alzheimer's disease 1

is ameliorated by CG9853^KK102820

(Wilson et al., 2024)

is exacerbated by Oari\PrP^VRQ.UAS

(Younan et al., 2018)

is exacerbated by Nmdmc^RNAi.UAS.cUa

(Yu et al., 2024)

is ameliorated by Nmdmc^UAS.Tag:HA

(Yu et al., 2024)

Comments on Models/Modifiers Based on Experimental Evidence ( 0 )

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Jahn et al., 2011)

This construct carries the amyloid Aβ42 peptide; variant described relative to the full-length protein and in terms of the Aβ42 peptide.

APP:p.Glu693Gly

(FlyBase curators, 2019-)

Variants Synonym(s)

APP(Aβ42 peptide):p.Glu22Gly

Associated human disease model(s)

External database links

ClinVar: APP_18098

Comments concerning this variant

Phenotypic Data

Phenotypic Class

Phenotype Manifest In

adult brain, with Scer\GAL4^elav-C155

(Kruppa et al., 2013)

eye, with Scer\GAL4^elav-C155

(Kruppa et al., 2013)

Detailed Description

Statement

Reference

Flies expressing Hsap\APP^{arctic.Aβ42.Scer\UAS.att} under the control of Scer\GAL4^elav-C155 exhibit significantly reduced rhythmicity in constant darkness (DD) compared to controls. The phenotype is from 2-12 days after eclosion onwards and progresses with increased age. Overall locomotor activity is unaffected. The flies exhibit the anticipatory ramping seen in control flies 2-3 hours prior to dusk or dawn in 12 hour light:dark conditions (LD). However, while control flies retain robust circadian behaviour when shifted to constant darkness (DD), the mutant flies become arrhythmic and are unable to re-synchronise within 24 hours of being shifted back to LD. A significantly reduced lifespan is seen compared to controls and, as in controls, lifespan is shorter in constant light conditions (LL) compared with LD. No loss of the LNv and ILNv clock neurons or the dorsal neuron groups LNd and DN1 is observed. Locomotor rhythm in DD is comparable to controls when Hsap\APP^{arctic.Aβ42.Scer\UAS.att} is expressed under the control of either Scer\GAL4^tim.PE or Scer\GAL4^P2.4.Pdf.

(Chen et al., 2014)

Median survival of flies expressing Scer\GAL4^elav-C155>Hsap\APP^{arctic.Aβ42.Scer\UAS.att} is 31 days compared with 66 days in control flies.

(Favrin et al., 2013)

Expression of Hsap\APP^{arctic.Aβ42.Scer\UAS.att} under the control of Scer\GAL4^elav-C155 results in the proliferation of AΒ plaques throughout the fly brain.

Expression of Hsap\APP^{Arctic.Aβ42.Scer\UAS.cJa.T:SS-nec} under the control of Scer\GAL4^elav-C155 results in the proliferation of AΒ plaques throughout the fly brain. These individuals display significant decreases in adul locomotion and in adult lifespan, as compared to controls.

(Kruppa et al., 2013)

Flies expressing Scer\GAL4^elav-C155>Hsap\APP^{arctic.Aβ42.Scer\UAS.att} become significantly and progressively impaired in their climbing ability. After day 10 the mutant flies are no longer able to climb the sides of the test tubes.

(Jahn et al., 2011)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

NOT Enhanced by

Statement

Reference

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has short lived phenotype, non-enhanceable by cue^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has abnormal neuroanatomy phenotype, non-enhanceable by cue^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has abnormal locomotor behavior phenotype, non-enhanceable by cue^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

Suppressed by

Statement

Reference

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has short lived phenotype, suppressible by Psa^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has abnormal neuroanatomy phenotype, suppressible by Psa^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has abnormal locomotor behavior phenotype, suppressible by Psa^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

NOT suppressed by

Statement

Reference

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has short lived phenotype, non-suppressible by cue^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has abnormal neuroanatomy phenotype, non-suppressible by cue^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has abnormal locomotor behavior phenotype, non-suppressible by cue^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

Phenotype Manifest In

NOT Enhanced by

Statement

Reference

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has adult brain phenotype, non-enhanceable by cue^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has eye phenotype, non-enhanceable by cue^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

Suppressed by

Statement

Reference

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has adult brain phenotype, suppressible by Psa^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has eye phenotype, suppressible by Psa^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

NOT suppressed by

Statement

Reference

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has adult brain phenotype, non-suppressible by cue^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}, Scer\GAL4^elav-C155 has eye phenotype, non-suppressible by cue^UAS.cKa, Scer\GAL4^elav-C155

(Kruppa et al., 2013)

Additional Comments

Genetic Interactions

Statement

Reference

Xenogenetic Interactions

Statement

Reference

Overexpression of CG14715^G6908 in Scer\GAL4^elav-C155>Hsap\APP^{arctic.Aβ42.Scer\UAS.att} flies results in a significant increase in climbing ability in early adulthood but has no effect on survival.

Co-expression of CG14715^GD4788 with Hsap\APP^{arctic.Aβ42.Scer\UAS.att} using Scer\GAL4^elav-C155 results in a significant increase in survival, but no improvement in climbing ability.

Co-expression of CG14715^KK104150 with Hsap\APP^{arctic.Aβ42.Scer\UAS.att} using Scer\GAL4^elav-C155 results in a significant increase in survival, but no improvement in climbing ability.

Co-expression of PGRP-SC1b^GD5490 using Scer\GAL4^elav-C155 ameliorates the Hsap\APP^{arctic.Aβ42.Scer\UAS.att} phenotypes: the flies show improved climbing and survival.

Co-expression of Sod3^GD4801 using Scer\GAL4^elav-C155 ameliorates the Hsap\APP^{arctic.Aβ42.Scer\UAS.att} phenotypes: the flies show improved climbing and survival.

(Favrin et al., 2013)

Co-expression of Psa^Scer\UAS.cKa results in an increase in median survival in flies expressing Hsap\APP^{arctic.Aβ42.Scer\UAS.att} under the control of Scer\GAL4^elav-C155. In addition, Psa^Scer\UAS.cKa expression suppresses the retinal toxicity associated with Hsap\APP^{arctic.Aβ42.Scer\UAS.att} expression, resulting in normal eye development. These flies are also functionally protected, as shown by improved locomotor function throughout their adult life, as compared to flies expressing Hsap\APP^{arctic.Aβ42.Scer\UAS.att} alone. Coexpression of Psa^Scer\UAS.cKa results in a marked reduction in the number of AΒ deposits.

Co-expression of cue^Scer\UAS.cKa does not affect the toxicity associated with expression of Hsap\APP^{arctic.Aβ42.Scer\UAS.att} under the control of Scer\GAL4^elav-C155.

(Kruppa et al., 2013)

Complementation and Rescue Data

Comments

Images (0)

Mutant

Wild-type

Stocks (0)

Notes on Origin

Discoverer

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (4)

Reported As

Symbol Synonym

Hsap\APP^{Arctic.Aβ42.Scer\UAS.cJa.T:SS-nec}

Hsap\APP^{Arctic.Aβ42.UAS.cJa.Tag:SS(nec)}

Hsap\APP^{arctic.Aβ42.Scer\UAS.att}

Hsap\APP^{arctic.Aβ42.Scer\UAS}

Name Synonyms

Secondary FlyBase IDs

References (11)

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