FlyBase Allele Report: Hsap\APP[695.UAS.Exel]

General Information

Symbol

Hsap\APP^695.UAS.Exel

Species

H. sapiens

Name

FlyBase ID

FBal0256652

Feature type

allele

Associated gene

Hsap\APP

Associated Insertion(s)

Carried in Construct

P{UAS-APP.695.Exel}

Also Known As

UAS-APP, UAS-APP₆₉₅, UAS-APP695

Key Links

Transgenic product class

wild_type

(Singh and Mahoney, 2011.2.17)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

wild_type

(Singh and Mahoney, 2011.2.17)

Mutagen

in vitro construct

(Singh and Mahoney, 2011.2.17)

Progenitor genotype

Carried in construct

P{UAS-APP.695.Exel}

Cytology

Description

UAS drives expression of the 695 amino acid isoform of Hsap\APP.

(Singh and Mahoney, 2011.2.17)

Allele components

Component

Use(s)

Regulatory region(s)

UAS

binary expression system - regulatory region

Encoded product / tool

Hsap\APP

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 with Hsap\BACE1^UAS.Exel

(da Costa Silva et al., 2022, Maggiore et al., 2022, Malta et al., 2022, Metsla et al., 2022, Vivien Chiu et al., 2017, Wang et al., 2015, Wang et al., 2014)

CEA

(Sarantseva et al., 2009)

CEA with Hsap\BACE1^UAS.Exel, Hsap\MAPT^UAS.VTR

(Yeh et al., 2018)

model of attention deficit hyperactivity disorder

CEA with Hsap\BACE1^UAS.Exel

(Zhang et al., 2015)

Modifiers Based on Experimental Evidence ( 0 )

Disease

Interaction

References

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

Disease-implicated variant(s)

Phenotypic Data

Phenotypic Class

abnormal learning | adult stage | progressive, with Scer\GAL4^elav-C155

(Sarantseva et al., 2009)

abnormal memory | adult stage | progressive, with Scer\GAL4^elav-C155

(Sarantseva et al., 2009)

abnormal neuroanatomy | adult stage | progressive, with Scer\GAL4^elav-C155

(Sarantseva et al., 2009)

Phenotype Manifest In

adult brain | progressive, with Scer\GAL4^elav-C155

(Sarantseva et al., 2009)

Detailed Description

Statement

Reference

Expression of Hsap\APP^{695.Scer\UAS.Exel} under the control of Scer\GAL4^elav-C155 results in age-progressive neurodegeneration as evidenced by the appearance of vacuolar lesions in the adult brain. The adult flies also display age-progressive learning and memory defects in an aversive olfactory memory assay.

(Sarantseva et al., 2009)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

NOT Enhanced by

Statement

Reference

Hsap\APP^695.UAS.Exel, Scer\GAL4^elav-C155 has abnormal neuroanatomy | adult stage | progressive phenotype, non-enhanceable by Hsap\BACE1^UAS.cGa, Scer\GAL4^elav-C155

(Sarantseva et al., 2009)

Suppressed by

Statement

Reference

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^elav-C155 has abnormal locomotor behavior | adult stage phenotype, suppressible by Hsap\GULP1^UAS.cVCa, Scer\GAL4^elav-C155

(Vivien Chiu et al., 2017)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^elav-C155 has short lived phenotype, suppressible by Hsap\GULP1^UAS.cVCa, Scer\GAL4^elav-C155

(Vivien Chiu et al., 2017)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^GMR.PF has decreased cell number | adult stage phenotype, suppressible by Hsap\GULP1^UAS.cVCa, Scer\GAL4^GMR.PF

(Vivien Chiu et al., 2017)

Enhancer of

Statement

Reference

Hsap\APP^695.UAS.Exel, Scer\GAL4^ninaE.PT is an enhancer of decreased cell number | adult stage | progressive phenotype of Hsap\BIN1^UAS.1, Scer\GAL4^ninaE.PT

(Lambert et al., 2022)

Suppressor of

Statement

Reference

Hsap\APP^695.UAS.Exel/Scer\GAL4^Appl.G1a is a suppressor of abnormal neuroanatomy | third instar larval stage phenotype of SNF4Aγ^loe

(Wentzell et al., 2012)

Other

Statement

Reference

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^elav-C155 has short lived phenotype

(Vivien Chiu et al., 2017)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^elav-C155 has abnormal locomotor behavior | adult stage phenotype

(Vivien Chiu et al., 2017)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^GMR.PF has decreased cell number | adult stage phenotype

(Vivien Chiu et al., 2017)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^elav.PLu has short lived phenotype

(Wang et al., 2015, Wang et al., 2014)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^elav.PLu has abnormal eclosion phenotype

(Wang et al., 2015)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^elav.PLu has abnormal locomotor behavior | progressive phenotype

(Wang et al., 2015, Wang et al., 2014)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^GMR.PF has visible | adult stage | progressive phenotype

(Wang et al., 2015)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^{elav.Switch.PO} has increased rate of movement | adult stage | RU486 conditional phenotype

(Zhang et al., 2015)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^{elav.Switch.PO} has increased rate of movement | adult stage phenotype

(Zhang et al., 2015)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^elav-C155 has decreased rate of movement | adult stage phenotype

(Zhang et al., 2015)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^GMR.PF has visible phenotype

(Wang et al., 2014)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.cGa, Scer\GAL4^elav-C155 has abnormal memory | adult stage | progressive phenotype

(Sarantseva et al., 2009)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.cGa, Scer\GAL4^elav-C155 has abnormal learning | adult stage | progressive phenotype

(Sarantseva et al., 2009)

Phenotype Manifest In

NOT Enhanced by

Statement

Reference

Hsap\APP^695.UAS.Exel, Scer\GAL4^elav-C155 has adult brain | progressive phenotype, non-enhanceable by Hsap\BACE1^UAS.cGa, Scer\GAL4^elav-C155

(Sarantseva et al., 2009)

Suppressed by

Statement

Reference

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^GMR.PF has ommatidium phenotype, suppressible by Hsap\GULP1^UAS.cVCa, Scer\GAL4^GMR.PF

(Vivien Chiu et al., 2017)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^GMR.PF has rhabdomere phenotype, suppressible by Hsap\GULP1^UAS.cVCa, Scer\GAL4^GMR.PF

(Vivien Chiu et al., 2017)

Enhancer of

Statement

Reference

Hsap\APP^695.UAS.Exel, Scer\GAL4^ninaE.PT is an enhancer of outer photoreceptor cell | adult stage | decreased number phenotype of Hsap\BIN1^UAS.1, Scer\GAL4^ninaE.PT

(Lambert et al., 2022)

Suppressor of

Statement

Reference

Hsap\APP^695.UAS.Exel/Scer\GAL4^Appl.G1a is a suppressor of larval brain | third instar larval stage phenotype of SNF4Aγ^loe

(Wentzell et al., 2012)

Other

Statement

Reference

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^GMR.PF has rhabdomere phenotype

(Vivien Chiu et al., 2017)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^GMR.PF has ommatidium phenotype

(Vivien Chiu et al., 2017, Wang et al., 2014)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^GMR.PF has eye | progressive phenotype

(Wang et al., 2015)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^GMR.PF has photoreceptor | adult stage | progressive phenotype

(Wang et al., 2015)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^GMR.PF has eye phenotype

(Wang et al., 2014)

Hsap\APP^695.UAS.Exel, Hsap\BACE1^UAS.Exel, Scer\GAL4^GMR.PF has retina phenotype

(Wang et al., 2014)

Additional Comments

Genetic Interactions

Statement

Reference

The co-expression of Hsap\BACE1^UAS.Exel and Hsap\APP^695.UAS.Exel under the control of Scer\GAL4^elav-C155 leads to significant decreases in adult climbing ability and in the number of rhabdomere per ommatidium, as compared to controls.

(Vivien Chiu et al., 2017)

Xenogenetic Interactions

Statement

Reference

Co-expression of Hsap\APP^{695.Scer\UAS.Exel} and Hsap\BACE1^{Scer\UAS.Exel} under the control of Scer\GAL4^GMR.PF results in age-progressive neurodegeneration (retinal collapse) and adult eye morphological defects including dark deposits in the eyes. Co-expression under the Scer\GAL4^elav.PLu driver does not affect pupariation rate but significantly decreases the eclosion rate of adult flies, leads to age-progressive deterioration of their climbing abilities and reduces the adult survival rate and median lifespan.

(Wang et al., 2015)

Co-expression of Hsap\APP^{695.Scer\UAS.Exel} and Hsap\BACE1^{Scer\UAS.Exel} driven by Scer\GAL4^{elav.Switch.PO} (with 200um RU486) results in significant hyperactivity (including nocturnal hyperactivity followed by a rapid decline, the effect is more prominent in male flies, and the effect disappears as flies age); this effect is more striking on a diet with a high carbohydrate to protein ratio (compared to low carbohydrate to protein ratio).

Co-expression of Hsap\APP^{695.Scer\UAS.Exel} and Hsap\BACE1^{Scer\UAS.Exel} driven by Scer\GAL4^elav-C155 results in significant hypoactivity compared to controls, though total activity at night is not significantly altered (it is significantly decreased during the day).

(Zhang et al., 2015)

Co-expression of Hsap\BACE1^{Scer\UAS.Exel} and Hsap\APP^{695.Scer\UAS.Exel} under the control of Scer\GAL4^GMR.PF results in a rough eye phenotype with disorganization of the retina, atrophy of ommatidia, and presence of abnormal amyloid deposits, as compared to controls.

Co-expression of Hsap\BACE1^{Scer\UAS.Exel} and Hsap\APP^{695.Scer\UAS.Exel} under the control of Scer\GAL4^elav.PLu leads to a significant decrease in lifespan and significant deterioration of climbing ability with age, as compared to controls.

(Wang et al., 2014)

Expression of Hsap\APP^{695.Scer\UAS.Exel} under the control of Scer\GAL4^Appl.G1a dramatically suppresses the increase in vacuolisation seen in the brains of SNF4Aγ^loe mutant third instar larvae.

Co-expression of Hsap\BACE1^Scer\UAS.cGa suppresses the increase in vacuolisation seen when Hsap\APP^{695.Scer\UAS.Exel} is expressed in the brains of SNF4Aγ^loe mutant third instar larvae under the control of Scer\GAL4^Appl.G1a.

(Wentzell et al., 2012)

The loss of tissue due to the age-progressive neurodegeneration (vacuolar lesions) observed in the brains of adult flies expressing Hsap\APP^{695.Scer\UAS.Exel} under the control of Scer\GAL4^elav-C155 is not significantly affected by co-expression of Hsap\BACE1^Scer\UAS.cGa. Flies expressing Hsap\APP^{695.Scer\UAS.Exel} either alone or in combination with Hsap\BACE1^Scer\UAS.cGa display strong age-progressive learning and memory defects.

(Sarantseva et al., 2009)

Complementation and Rescue Data

Comments

Images (0)

Mutant

Wild-type

Stocks (8)

Bloomington

33796

w¹¹¹⁸; P{UAS-APP.695.Exel}3

33795

y¹ w¹¹¹⁸; P{UAS-APP.695.Exel}5