FB2025_01 , released February 20, 2025
Allele: Dmel\foxo21
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General Information
Symbol
Dmel\foxo21
Species
D. melanogaster
Name
FlyBase ID
FBal0151930
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
dFOXO21
Key Links
Genomic Maps

Nature of the Allele
Progenitor genotype
Associated Insertion(s)
Cytology
Description

The progenitor P{EP}EP35-147 insertion is also still present on the chromosome.

Amino acid replacement: W95term.

Allele components
Component
Use(s)
Mutations Mapped to the Genome
Curation Data
Type
Location
Additional Notes
References
Nucleotide change:

G14067001A

Amino acid change:

W95term | foxo-PB; W95term | foxo-PC; W95term | foxo-PF; W95term | foxo-PG; W95term | foxo-PH

Reported amino acid change:

W95term

Comment:

G to A nucleotide change at the second or third position of the Trp codon leads to a nonsense mutation. (exact site of mutation unspecified). Site of nucleotide substitution in mutant inferred by FlyBase based on reported amino acid change.

Variant Molecular Consequences
Associated Sequence Data
DNA sequence
Protein sequence
 
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 ( 0 )
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 1 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

foxo21/foxo25 mutant testes contain significantly more undifferentiated germ cells compared to heterozygous controls.

foxo21/foxo25 mutant germaria show increased germline stem cell loss following irradiation compared with controls.

Adult brains have a significant decrease in dopaminergic neuron number (especially in the DL1 cluster) in 30 day old foxo21/foxo25 flies. Climbing ability in foxo21/foxo25 is significantly worse (at both 3 and even more so at 15 days old) and there is a significant reduction in ATP of the indirect flight muscle compared to wild type at 15 (but not 3) days old.

foxo21 mutant embryos do not exhibit aberrant cell fate specification or axon guidance defects. foxo21 mutant third instar larvae are indistinguishable from wild-type with respect to overall body size and muscle area and display no appreciable change in bouton number. However, the area of individual type 1b boutons is significantly increased. In addition, there is an increase in the number of closed, tightly bundled futsch-positive microtubule loops at neuromuscular junction 6/7.

foxo21 mutant neuromuscular junctions display enhanced microtubule stability compared to controls.

foxo21 mutants display impaired synaptic vesicle dynamics (assayed through FM 1-43 dye).

foxo21/foxo25 flies are short lived relative to wild-type controls, but their lifespan patterns responding to diet are similar to their wild-type controls.

The shift to a more acidic pH of fecal excreta which is seen in wild-type flies in response to a low-calorie diet does not occur in foxo21/Df(3R)Exel8159 flies.

foxo21/foxo25 mutant animals display accelerated muscle aging manifesting in the increased accumulation of age-related protein aggregates compared with wild-type flies.

foxo21/foxo25 transheterozygous larvae exhibit reduced survival and shorter life span under amino acid starvation conditions. These flies are also developmentally delayed under these conditions and are smaller than wild-type after 48 hours.

Starvation-induced autophagy is strongly reduced compared to controls in foxo21/foxo25 larvae.

foxo21/foxo25 mutants rapidly become arrythmic in the presence of low levels of paraquat (0.5-1mM), while wild-type flies retain their rhythms for a few weeks. Phototaxis is not affected by paraquat treatment in these mutants.

foxo21/foxo25 mutant flies are hypersensitive to oxidative stress.

30 day old foxo21/foxo25 mutant flies show weak rhythms simliar to those seen in response to paraquat in young flies.

foxoBG01018/foxo21 flies display a 4.8% improvement in medial survival following M.marinum infection in comparison to wild-type flies - 174 hours vs. 166 hours. foxo21/foxo25 transheterozygotes survive even longer - 190 hours following infection. The number of bacteria recorded in these flies is not significantly different from wild-type flies.

Homozygous mutant animals do not exhibit a a detectable growth phenotype.

foxo21/foxo25 flies exhibit a reduced life-span when exposed to 5% hydrogen peroxide-containing media (median life-span of 34.5 hours). Only 2% of foxo21/foxo25 flies survived 60 hours after exposure to oxidative stress, compared to 66.1% in wild-type.

Shows no obvious phenotype under normal culturing conditions, though close inspection reveals the wing size is slightly reduced. Clonal analysis in the head capsule reveals no effect on growth. Clonal analysis reveals no difference of cell size in the developing eye between mutant and wild type. No significant difference between body weight of mutant and wild type flies is detectable. When placed on hydrogen-peroxide-containing food mutant flies display significantly reduced survival time compared to control flies. A similar effect occurs in response to paraquat feeding.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
NOT Enhanced by
Statement
Reference
Suppressed by
Enhancer of
Statement
Reference
NOT Enhancer of
Statement
Reference
Suppressor of
Statement
Reference

foxo25/foxo21 is a suppressor of abnormal oxidative stress response | adult stage | chemical conditional phenotype of Trap1EY21851

foxo21/foxo[+] is a suppressor of visible phenotype of Hsap\APLP1UAS.cMa, Scer\GAL4sd-SG29.1

foxo21/foxo[+] is a suppressor of visible phenotype of Hsap\APLP1UAS.cMa, Scer\GAL4pnr-MD237

foxo21/foxo[+] is a suppressor of abnormal size phenotype of IdeGD6073, Scer\GAL4en-e16E

foxo21/foxo[+] is a suppressor of lethal phenotype of Hsap\APPAβ42.UAS.cUa, Scer\GAL4elav.PU

foxo21/foxo[+] is a suppressor | partially of short lived | RU486 conditional phenotype of Scer\GAL4elav.Switch.PO, forP1.UAS

foxo21/foxo[+] is a suppressor | partially of abnormal locomotor behavior | adult stage | RU486 conditional phenotype of Scer\GAL4elav.Switch.PO, forP1.UAS

foxo21/foxo[+] is a suppressor | partially of visible phenotype of Cln3UAS.cTa, Scer\GAL4GMR.PF

foxo21/foxo[+] is a suppressor of long lived | dominant phenotype of 14-3-3εj2B10

foxo21/foxo[+] is a suppressor of long lived | dominant phenotype of pucE69

foxo21/foxo[+] is a suppressor of decreased cell number phenotype of chicoflp147E/chico1

foxo21/foxo[+] is a suppressor of visible phenotype of chicoflp147E/chico1

foxo25/foxo21 is a suppressor of visible phenotype of chicoflp147E/chico1

foxo25/foxo21 is a suppressor of lethal | larval stage phenotype of Akt1

NOT Suppressor of
Statement
Reference
Other
Phenotype Manifest In
NOT Enhanced by
Statement
Reference
Suppressed by
Statement
Reference

foxo21 has synaptic vesicle phenotype, suppressible by futschK68/futsch[+]

foxo21 has microtubule phenotype, suppressible by futschK68/futsch[+]

foxo21 has microtubule phenotype, suppressible by futschN94/futsch[+]

Enhancer of
Statement
Reference
NOT Enhancer of
Statement
Reference

foxo25/foxo21 is a non-enhancer of adult thorax phenotype of Pink1B9

foxo25/foxo21 is a non-enhancer of mitochondrion | adult stage phenotype of Pink1B9

foxo25/foxo21 is a non-enhancer of wing blade phenotype of Pink1B9

Suppressor of
Statement
Reference

foxo25/foxo21 is a suppressor of escort cell phenotype of InRE19/InR339

foxo21/foxo[+] is a suppressor | partially of wing phenotype of IdeUAS.cGa, Scer\GAL4Bx-MS1096-KE

foxo21/foxo[+] is a suppressor | partially of wing phenotype of IdeUAS.cGa, Scer\GAL4en-e16E

foxo21 is a suppressor of wing phenotype of DaxxEY09290, Scer\GAL4Bx-MS1096

foxo21/foxo[+] is a suppressor of eye phenotype of Hsap\APPAβ42.GMR.Tag:SS(rPENK)

foxo21/foxo[+] is a suppressor | partially of eye phenotype of Cln3UAS.cTa, Scer\GAL4GMR.PF

foxo21/foxo[+] is a suppressor of eye phenotype of Scer\GAL4sev.EP, hepAct.UAS

foxo21/foxo[+] is a suppressor of ommatidium phenotype of chicoflp147E/chico1

foxo21/foxo[+] is a suppressor of wing phenotype of chicoflp147E/chico1

foxo25/foxo21 is a suppressor of wing phenotype of chicoflp147E/chico1

NOT Suppressor of
Statement
Reference
Additional Comments
Genetic Interactions
Statement
Reference

The decreased number of escort cells observed in the germarium of InRE19/InR339 transheterozygotes is suppressed by additional foxo21/foxo25 transheterozygosity.

Presence of foxo25/foxo21 significantly suppresses increased survival in response to rotenone or paraquat in Trap1EY21851/Trap1EY21851 flies. foxo21/+ partially suppresses rescue of locomotor defects by Trap1EY21851/Trap1EY21851 in Pink1B9/Pink1B9 flies. Presence of foxo25/foxo21 suppresses rescue via feeding of G-TTP of locomotor defects in Pink1B9/Pink1B9 flies.

The reduced wing phenotype caused by expression of DLPEY09290 under the control of Scer\GAL4Bx-MS1096 is suppressed by foxo21.

The defect in climbing ability and reduction in lifespan seen in flies expressing forP1.Scer\UAS under the control of Scer\GAL4elav.Switch.PO in the presence of RU486 is partially suppressed by foxo21/+.

Expression of Sirt1Scer\UAS.cGa driven by Scer\GAL4arm.PU partially suppresses phenotypes (collapsed thorax, downturned wings, swollen mitochondria along with increased cell death and reduced levels of mtDNA and ATP in the indirect flight muscle and locomotor defects) seen in (3 day old) Pink1B9/Y flies. Presence of foxo25/foxo21 almost completely nullifies the suppressive effect of Scer\GAL4arm.PU>Sirt1Scer\UAS.cGa on phenotypes in Pink1B9/Y flies.

foxo25/foxo21 does not significantly enhance phenotypes (collapsed thorax, downturned wings, swollen mitochondria along with increased cell death and reduced levels of mtDNA and ATP in the indirect flight muscle and locomotor defects) seen in Pink1B9/Y flies.

Pink1B9/Y does not enhance dopaminergic neuron loss (in the DL1 cluster) in foxo21/foxo25 flies.

A futschK68/+ background suppresses the increase in type 1b bouton area observed in foxo21 homozygotes. Furthermore, this background dominantly suppresses the elevated number of microtubule loops present in foxo21 mutants.

A futschN94 background dominantly suppresses the elevated number of microtubule loops present in foxo21 mutants.

A futschK68/+ background suppresses the FM 1-43 loading defects found in foxo21 mutant synapses.

foxo21 does not rescue the reduced body weight of Lst81 flies.

The eye phenotype resulting from the overexpression of cln3Scer\UAS.cTa under the control of Scer\GAL4GMR.PF is partially suppressed by foxo21/+.

Lipid levels are completely restored in Sik348 ; foxo21/foxo25 double mutant flies.

Overexpression of ThorLL.Scer\UAS under the control of Scer\GAL4Mhc.PW in a heterozygous foxo21 mutant genetic background is sufficient to significantly extend longevity compared with wild type by increasing the median and maximum life span of flies.

The 'food-leaving' behaviour of forR, foxo21 flies is not significantly different from forR flies.

The lifespan of 14-3-3εj2B10/+, foxo21/+ double heterozygous flies is similar to wild-type levels.

Removal of both copies of foxo (foxo25/foxo21) is lethal in TORC25-3 homozygotes.

TORCScer\UAS.cWa over-expressing flies (driven by Scer\GAL4GMR.PF) in which foxo is reduced or eliminated though a foxo25/foxo21 background still exhibit a rough eye phenotype.

Ectopic expression of ThorScer\UAS.cTa, under the control of Scer\GAL4Act5C can completely suppress the sensitivity of foxo21/foxo25 flies to oxidative stress (median life-span of 56.8 hours, 39.7% survival rate after 60 hours exposure to 5% hydrogen peroxide).

The increase in average and maximum lifespan seen in pucE69/+ adults is dominantly suppressed by foxo21.

Xenogenetic Interactions
Statement
Reference

foxo21/+ significantly partially suppresses the increased cell death induced by expression of Hsap\APLP1Scer\UAS.cMa driven along the anterior/posterior compartment boundary in third instar larval wing discs by Scer\GAL4ptc-559.1, suppresses the blistered wing phenotype in flies with expression of Hsap\APLP1Scer\UAS.cMa driven by Scer\GAL4sd-SG29.1, and suppresses the small scutellum phenotype seen with expression of Hsap\APLP1Scer\UAS.cMa driven by Scer\GAL4pnr-MD237.

The ability of 0.5mM Psammaplysene A to suppress the eye degeneration phenotype caused by expression of Hsap\ARQ52.Scer\UAS under the control of Scer\GAL4GMR.PU (in the presence of dihydrotestosterone) is suppressed if the flies are also heterozygous for foxo21.

Complementation and Rescue Data
Comments

Expression of foxoT:SV5\V5 rescues the circadian arrhythmia seen in foxo21/foxo25 mutants. Phototaxis is not affected by paraquat treatment in these mutants.

Expression of foxoScer\UAS.cFa under the control of Scer\GAL4Lk6-DJ634 rescues the circadian arrhythmia seen in foxo21/foxo25 mutants. Phototaxis is not affected by paraquat treatment in these mutants.

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Mutant
Wild-type
Stocks (3)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (13)
References (54)