FlyBase Allele Report: Dmel\Appl[d]

General Information

Symbol

Dmel\Appl^d

Species

D. melanogaster

Name

FlyBase ID

FBal0028990

Feature type

allele

Associated gene

Dmel\Appl

Associated Insertion(s)

Carried in Construct

Key Links

Allele class

amorphic allele - genetic evidence

loss of function allele

Mutagen

gamma ray

Nature of the Allele

Allele class

amorphic allele - genetic evidence

(Luo et al., 1992)

loss of function allele

(Ashley et al., 2005)

Mutagen

gamma ray

(Luo et al., 1992)

Progenitor genotype

Df(1)yT7-518

(Luo et al., 1992)

Dp(1;Y)y⁺m⁶⁴

(Luo et al., 1992)

Cytology

Description

Interstitial deletion of the central region of the Appl gene.

(Torroja et al., 1996)

Generated by translocation of distal part of Dp(1;Y)y⁺m⁶⁴ onto proximal part of Df(1)yT7-518. Deletion of central portion of Appl gene. Exon containing translational start site and exon containing stop codon retained.

(Luo et al., 1992)

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

(Bourdet et al., 2015, Bourdet et al., 2015)

model of Alzheimer's disease 1

CEA

(Nath and Lee, 2025, Kessissoglou et al., 2020, Penserga et al., 2019, Rieche et al., 2018, Sone et al., 2009)

CEA with Appl^f03252

(Rieche et al., 2018)

CEA with Appl^f04460

(Rieche et al., 2018)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of Alzheimer's disease

is exacerbated by Bace^UAS.cCSa

(Bourdet et al., 2015)

is exacerbated by kuz^UAS.cFa

(Bourdet et al., 2015)

ameliorates autosomal recessive intellectual developmental disorder

modeled by Nab2^ex3

(Corgiat et al., 2022)

exacerbates neurodegenerative disease

modeled by SNF4Aγ^loe

(Tschäpe et al., 2002)

model of Alzheimer's disease 1

is ameliorated by Rab5^KO

(Kessissoglou et al., 2020)

is exacerbated by Rab7^Gal4-KO

(Kessissoglou et al., 2020)

is ameliorated by Fas2^GD14486

(Rieche et al., 2018)

is ameliorated by Fas2^e76

(Rieche et al., 2018)

is ameliorated by AMPKα^TD.UAS

(Nath and Lee, 2025)

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

Disease-implicated variant(s)

Phenotypic Data

Phenotypic Class

Phenotype Manifest In

Detailed Description

Statement

Reference

Most Appl^d adults exhibit giant fibers with pruning defects, although it is not associated with synaptic transmission defects (10 trains of 10 stimulations at 100 Hz).

(Penserga et al., 2019)

Appl^d mutants carrying Scer\GAL4^{Mef2.247.Switch} exhibit an impairment in electric shock avoidance, as well as an apparent defect in learning that could result from the impairment in shock relativity.

Appl^d/+; Scer\GAL4^{Mef2.247.Switch}/+ heterozygous flies exhibit a LTM impairment and a slight but significant STM defect compared with wild-type.

Appl^d/+; Scer\GAL4^{Mef2.247.Switch}/+ heterozygous flies exhibit wild-type shock reactivity, wild-type olfactory acuity and normal learning.

(Bourdet et al., 2015)

Appl^d/+ flies have significant defects in short term memory (2hr) compared to controls in an olfactory aversive conditioning paradigm, but show normal learning, olfactory acuity and shock reactivity.

Adult specific expression of Appl^{Aβ.Scer\UAS.T:Ivir\HA1} driven by Scer\GAL4^{Mef2.247.Switch} (activated in adult flies fed RU486) significantly enhances short term memory defects in Appl^d/+ flies (compared to Appl^d/+ flies or to controls not fed RU486); there are no significant effects on learning, olfactory acuity or shock reactivity.

(Bourdet et al., 2015)

No vacuole formation is seen in the brains of Appl^d mutant flies up to 14 days old. However, some vacuoles are detected in the brains of 4 week old flies. This phenotype occurs with full penetrance and vacuoles are not seen in age matched controls. The lifespan of Appl^d mutant flies is significantly shortened; females live up to a maximum of 54 days compared to 54 days in controls and males only live to a maximum of 40 days compared to 102 days in controls. 7% of male and female flies have died by 8 days, compared to only 1% and 2% of females and males respectively.

(Wentzell et al., 2012)

Homozygous and Appl^d/Df(1)vnd^D38 adults have a normal central brain volume at 0 days after eclosion.

(Sone et al., 2009)

Mutants show loss of the scutellar macrochaetae.

(Kim et al., 2007)

EJC amplitude in Appl^d larvae is reduced compared to wild-type.

Appl^d larvae show enhanced post-tetantic potentiation.

(Rusu et al., 2007)

Appl^d heterozygotes exhibit a reduction in bouton number.

Appl^d mutants exhibit a significant decrease in EJP amplitude compared to wild-type.

(Ashley et al., 2005)

Appl^d flies do not show significantly impaired survival under standard conditions. However, these flies show a large increase in mortality compared to wild-type flies 1 and 2 weeks after brain trauma.

(Leyssen et al., 2005)

Mutant animals show a reduction in the number of scutellar and sternopleural mechanosensory organs.

(Merdes et al., 2004)

Homozygous mutant larvae exhibit organelle accumulation within neurons. However the larvae are viable and do not exhibit tail flipping or paralysis.

(Gunawardena and Goldstein, 2001)

NMJs from mutant larvae have a generally normal appearance but have 34% fewer boutons than wild type at muscles 6 and 7 of abdominal segment 3. Total number of synaptic boutons (muscles 6 and 7 (abdominal segment 3)) is decreased, percentage of satellite boutons is decreased and the number of normal boutons is decreased. When Appl^sd.Scer\UAS expression is driven in the motoneurons muscles 6 and 7 (abdominal segment 3) in combination with Appl^d total number of synaptic boutons is increased, percentage of satellite boutons is increased and the number of normal boutons is increased.

(Torroja et al., 1999)

No morphological defects either externally or in parafin sections of heads. Abnormal fast phototactic response, not due to simple locomotor defect.

(Luo et al., 1992)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhanced by

Statement

Reference

Appl^d has abnormal memory phenotype, enhanceable by kuz^UAS.cFa/Scer\GAL4^{Mef2.247.Switch}

(Bourdet et al., 2015)

Appl^d has abnormal memory | adult stage phenotype, enhanceable by Scer\GAL4^{Mef2.247.Switch}/Bace^UAS.cCSa

(Bourdet et al., 2015)

Appl^d has abnormal memory | adult stage phenotype, enhanceable by Scer\GAL4^c739/Bace^UAS.cCSa

(Bourdet et al., 2015)

NOT Enhanced by

Statement

Reference

Appl^d has abnormal learning phenotype, non-enhanceable by kuz^UAS.cFa/Scer\GAL4^{Mef2.247.Switch}

(Bourdet et al., 2015)

Suppressed by

Statement

Reference

Appl^d, SNF4Aγ^loe has abnormal neuroanatomy | third instar larval stage phenotype, suppressible | partially by Scer\GAL4^Appl.G1a/Appl^UAS.cCSa

(Wentzell et al., 2012)

Appl^d has visible phenotype, suppressible by APP-BP1[+]/APP-BP1^Ex62

(Kim et al., 2007)

NOT suppressed by

Statement

Reference

Appl^d, SNF4Aγ^loe has abnormal neuroanatomy | third instar larval stage phenotype, non-suppressible by Appl^s.UAS.Tag:HA/Scer\GAL4^Appl.G1a

(Wentzell et al., 2012)

Appl^d has visible phenotype, non-suppressible by APP-BP1[+]/APP-BP1^Ex183

(Kim et al., 2007)

Enhancer of

Statement

Reference

Appl^d is an enhancer of abnormal neuroanatomy | adult stage phenotype of SNF4Aγ^loe

(Wentzell et al., 2012)

Appl^d/Df(1)vnd^D38 is an enhancer of short lived phenotype of yata^KE2.1

(Sone et al., 2009)

NOT Enhancer of

Statement

Reference

Appl^d is a non-enhancer of decreased cell number | adult stage | progressive phenotype of Hsap\BIN1^UAS.1, Scer\GAL4^ninaE.PT

(Lambert et al., 2022)

Appl^d/Appl[+] is a non-enhancer of abnormal neuroanatomy | adult stage | dominant phenotype of tap^Gal4

(Yuan et al., 2016)

Suppressor of

Statement

Reference

Appl^d/Appl[+] is a suppressor | partially of visible | adult stage phenotype of Nab2^EP3716, Scer\GAL4^GMR.PU

(Lee et al., 2020)

Appl^d/Appl[+] is a suppressor | partially of increased mortality during development phenotype of Nab2^ex3

(Lee et al., 2020)

Appl^d is a suppressor of abnormal neuroanatomy | adult stage | progressive phenotype of Bace^GD5366, Scer\GAL4^GMR.PU

(Bolkan et al., 2012)

Appl^d is a suppressor of abnormal neurophysiology phenotype of Fas2^e76

(Ashley et al., 2005)

NOT Suppressor of

Statement

Reference

Appl^d is a non-suppressor of decreased cell number | adult stage | progressive phenotype of Hsap\BIN1^UAS.1, Scer\GAL4^ninaE.PT

(Lambert et al., 2022)

Appl^d is a non-suppressor of abnormal neuroanatomy phenotype of Scer\GAL4^P2.4.Pdf, hep^CA.UAS

(Leyssen et al., 2005)

Phenotype Manifest In

Suppressed by

Statement

Reference

Appl^d has larval multidendritic class IV neuron | somatic clone phenotype, suppressible by Dscam1^{4.3-6.36-9.25-17.2}/Scer\GAL4^ppk.PU

(Pizzano et al., 2023)

Appl^d has axon | somatic clone | larval stage phenotype, suppressible by Dscam1^{4.3-6.36-9.25-17.2}/Scer\GAL4^ppk.PU

(Pizzano et al., 2023)

Appl^d, SNF4Aγ^loe has larval brain | third instar larval stage phenotype, suppressible | partially by Scer\GAL4^Appl.G1a/Appl^UAS.cCSa

(Wentzell et al., 2012)

Appl^d has anterior scutellar bristle phenotype, suppressible by APP-BP1[+]/APP-BP1^Ex62

(Kim et al., 2007)

Appl^d has NMJ bouton phenotype, suppressible by Fas2^UAS.cAa/Scer\GAL4^C164

(Ashley et al., 2005)

Appl^d has NMJ bouton phenotype, suppressible by Fas2^UAS.cAa/Scer\GAL4^C57

(Ashley et al., 2005)

NOT suppressed by

Statement

Reference

Appl^d, SNF4Aγ^loe has larval brain | third instar larval stage phenotype, non-suppressible by Appl^s.UAS.Tag:HA/Scer\GAL4^Appl.G1a

(Wentzell et al., 2012)

Appl^d has posterior scutellar bristle phenotype, non-suppressible by APP-BP1[+]/APP-BP1^Ex62

(Kim et al., 2007)

Appl^d has anterior scutellar bristle phenotype, non-suppressible by APP-BP1[+]/APP-BP1^Ex183

(Kim et al., 2007)

Appl^d has posterior scutellar bristle phenotype, non-suppressible by APP-BP1[+]/APP-BP1^Ex183

(Kim et al., 2007)

Enhancer of

Statement

Reference

Appl^d is an enhancer of adult brain phenotype of SNF4Aγ^loe

(Wentzell et al., 2012, Tschäpe et al., 2002)

NOT Enhancer of

Statement

Reference

Appl^d is a non-enhancer of outer photoreceptor cell | adult stage | decreased number phenotype of Hsap\BIN1^UAS.1, Scer\GAL4^ninaE.PT

(Lambert et al., 2022)

Appl^d/Appl[+] is a non-enhancer of adult mushroom body alpha-lobe | adult stage phenotype of tap^Gal4

(Yuan et al., 2016)

Suppressor of

Statement

Reference

Appl^d/Appl[+] is a suppressor | partially of eye phenotype of Nab2^EP3716, Scer\GAL4^GMR.PU

(Lee et al., 2020)

Appl^d is a suppressor of cell body rind of adult lamina | progressive phenotype of Bace^GD5366, Scer\GAL4^GMR.PU

(Bolkan et al., 2012)

Appl^d is a suppressor of NMJ bouton phenotype of Fas2^e76

(Ashley et al., 2005)

NOT Suppressor of

Statement

Reference

Appl^d is a non-suppressor of outer photoreceptor cell | adult stage | decreased number phenotype of Hsap\BIN1^UAS.1, Scer\GAL4^ninaE.PT

(Lambert et al., 2022)

Appl^d is a non-suppressor of ventral adult lateral neuron & axon phenotype of Scer\GAL4^P2.4.Pdf, hep^CA.UAS

(Leyssen et al., 2005)

Appl^d is a non-suppressor of ventral adult lateral neuron & axon phenotype of Abl::Hsap\ABL1::Hsap\BCR^P210.UAS, Scer\GAL4^P2.4.Pdf

(Leyssen et al., 2005)

Other

Statement

Reference

Appl^d/Df(1)vnd^D38, yata^KE2.1 has supraesophageal ganglion phenotype

(Sone et al., 2009)

Appl^d, Fas2^e76 has NMJ bouton phenotype

(Ashley et al., 2005)

Additional Comments

Genetic Interactions

Statement

Reference

Appl^d/+ does not significantly enhance frequency of mushroom body beta lobe axon overgrowth defects in tap^Gal4/+ brains.

(Yuan et al., 2016)

Expression of kuz^Scer\UAS.cFa in a Appl^d/+; Scer\GAL4^{Mef2.247.Switch} heterozygous background exacerbates the short term memory deficit found in this background. These flies exhibit this exacerbated defect regardless of whether the flies are fed with RU for 48 hours before conditioning. Appl^d/+; Scer\GAL4^{Mef2.247.Switch}/kuz^Scer\UAS.cFa flies fed with RU and testing immediately after conditioning exhibit wild-type learning. The ability to avoid electric shocks as well as their olfactory acuity to each odour after electric shock exposure is unaffected.

(Bourdet et al., 2015)

Adult specific expression of Bace^{Scer\UAS.cCSa} driven by Scer\GAL4^{Mef2.247.Switch} (activated in adult flies fed RU486) significantly enhances short term memory defects in an olfactory aversive conditioning paradigm compared to Appl^d/+ flies or to controls not fed RU486; there are no significant effects on learning, olfactory acuity or shock reactivity.

Adult specific expression of Bace^{Scer\UAS.cCSa} driven by Scer\GAL4^c739 (using the TARGET system) significantly enhances short term memory defects in an olfactory aversive conditioning paradigm compared to Appl^d/+ flies or to genetic or temperature controls; there are no significant effects on learning, olfactory acuity or shock reactivity.

(Bourdet et al., 2015)

Hemizygosity for Appl^d enhances the vacuolisation seen in 4 day old SNF4Aγ^loe mutant males.

Expression of Appl^{Scer\UAS.cCSa} under the control of Scer\GAL4^Appl.G1a partially suppresses the vacuolisation seen in 4 day old Appl^d SNF4Aγ^loe double mutant males, returning the phenotype to the level seen in SNF4Aγ^loe single mutants.

Expression of Appl^{s.Scer\UAS.T:Ivir\HA1} under the control of Scer\GAL4^Appl.G1a fails to suppress the vacuolisation seen in 4 day old Appl^d SNF4Aγ^loe double mutant males.

(Wentzell et al., 2012)

yata^KE2.1/yata^KE2.1 Appl^d/Df(1)vnd^D38 double mutant adults show a significant reduction in central brain volume at 0 days after eclosion.

The reduction in lifespan seen in yata^KE2.1 homozygous adults is more severe if the flies are also carrying Appl^d/Df(1)vnd^D38.

(Sone et al., 2009)

The loss of anterior scutellar macrochaetae that is seen in Appl^d flies is partially suppressed by APP-BP1^Ex62/+, but is not suppressed by APP-BP1^Ex183/+. The loss of posterior scutellar macrochaetae that is seen in Appl^d flies is not suppressed by APP-BP1^Ex62/+ or APP-BP1^Ex183/+.

(Kim et al., 2007)

Overexpression of Fas2^Scer\UAS.cAa in both presynaptic and postsynaptic cells (under the control of Scer\GAL4^C164 and Scer\GAL4^C57) in Appl^d mutants leads to a wild-type number of boutons, in contrast to the two-fold increase when Appl levels are normal.

The increase in bouton number in Fas2^e76/+ heterozygotes is completely suppressed in Appl^d homozygous mutants. Indeed, the number of synaptic boutons is lower than in wild-type.

The increased EJP amplitude in Fas2^e76/+ heterozygotes is completely suppressed in the absence of Appl in Appl^d, Fas2^e76/+ mutants. The EJP is indistinguishable from Appl^d/+ mutants.

(Ashley et al., 2005)

Expression of hep^CA.Scer\UAS, under the control of Scer\GAL4^P2.4.Pdf, in an Appl^d mutant background still induces the significant axonal extension seen when the transgene is expressed in a wild-type background.

(Leyssen et al., 2005)

The addition of Appl^d enhances the adult brain degeneration phenotype seen in SNF4Aγ^loe animals.

(Tschäpe et al., 2002)

Xenogenetic Interactions

Statement

Reference

Expression of Abl::Hsap\ABL1::Hsap\BCR^{P210.Scer\UAS}, under the control of Scer\GAL4^P2.4.Pdf, in a Appl^d background still induces the axonal arborization phenotype that occurs when the transgene is expressed in a wild-type background.

(Leyssen et al., 2005)

Complementation and Rescue Data

Rescued by

Appl^d/Appl[+] is rescued by Scer\GAL4^{Mef2.247.Switch}/Appl^UAS.cTa

(Bourdet et al., 2015)

Appl^d is rescued by Appl^s.UAS/Scer\GAL4^{Mef2.247.Switch}

(Bourdet et al., 2015)

Appl^d is rescued by Scer\GAL4^{Mef2.247.Switch}/Appl^sd.UAS

(Bourdet et al., 2015)

Partially rescued by

Appl^d is partially rescued by Scer\GAL4^sca-537.4/Appl^UAS.cTa

(Merdes et al., 2004)

Appl^d is partially rescued by Appl^hs.PL

(Luo et al., 1992)

Not rescued by

Appl^d is not rescued by Appl^s.UAS/Scer\GAL4^{Mef2.247.Switch}

(Bourdet et al., 2015)

Appl^d is not rescued by Scer\GAL4^{Mef2.247.Switch}/Appl^sd.UAS

(Bourdet et al., 2015)

Appl^d is not rescued by Appl^sd.hs

(Luo et al., 1992)

Comments

Expression of wild-type Appl^Scer\UAS.cTa in the mushroom bodies, under the RU-fed control of Scer\GAL4^{Mef2.247.Switch} rescues the STM deficit found in Appl^d/+ ; Scer\GAL4^{Mef2.247.Switch} flies.

Expression of Appl^s.Scer\UAS in a heterozygous Appl^d/+;Scer\GAL4^{Mef2.247.Switch} background suppresses the short term memory defect seen in this background, even in flies that have not been fed RU.

RU-induced expression of Appl^sd.Scer\UAS under the control of Scer\GAL4^{Mef2.247.Switch} fails to rescue the long term memory deficit caused by Appl^d/+ partial loss-of-function.

Expression of Appl^sd.Scer\UAS in RU-fed flies suppresses the short-term memory defect found in Appl^d/+; Scer\GAL4^{Mef2.247.Switch} flies. In contrast, in the absence of RU-feeding, Appl^d/+; Scer\GAL4^{Mef2.247.Switch}/Appl^sd.Scer\UAS flies exhibit scores that are indistinguishable from controls and significantly lower than that found in wild-type flies.

RU-induced expression of Appl^sd.Scer\UAS under the control of Scer\GAL4^{Mef2.247.Switch} fails to rescue the long term memory deficit caused by Appl^d/+ partial loss-of-function.

(Bourdet et al., 2015)

Images (0)

Mutant

Wild-type

Stocks (1)

Bloomington

43632

Appl^d w^*

Notes on Origin

Discoverer

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (7)

Reported As

Symbol Synonym

APPL^d

(Rusu et al., 2007)

Appl deletion

(Gunawardena and Goldstein, 2001)

Appl {d}

(Mhatre et al., 2014)

Appl^-

(Gunawardena and Goldstein, 2001)

appl^D

(Restrepo et al., 2022)

appl^d

(Song and Broadie, 2023, Corgiat et al., 2022, Walsh et al., 2021, Kessissoglou et al., 2020, Leyssen et al., 2005, Merdes et al., 2004)

Name Synonyms

Secondary FlyBase IDs

References (36)

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