Allele Dmel\foxo²¹

General Information
Symbol	Dmel\foxo²¹	Species	D. melanogaster
Name		FlyBase ID	FBal0151930
Feature type	allele	Associated gene	Dmel\foxo
Also Known As	dFOXO²¹

Map ( GBrowse )
Allele class	loss of function allele
Mutagen	P-element activity
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
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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.
Nature of the Allele
Allele class	loss of function allele (Dionne et al., 2006)
Mutagen	P-element activity (Junger et al., 2003)
Mutations Mapped to the Genome

Type Location Additional Notes References point mutation 3R:9,892,723..9,892,723 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. evidence=experimental pr_change=W95\|foxo-PC,W95\|foxo-PA,W95@\|foxo-PB reported_pr_change=W95@ na_change=G9892723A (Junger et al., 2003)
Associated Sequence Data
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name

UniProtKB/Swiss-Prot
UniProtKB/TrEMBL

Progenitor genotype	foxo^EP35-147 (Junger et al., 2003)
Nature of the lesion	Statement Reference Amino acid replacement: W95@. (Junger et al., 2003)
Caused by insertion	P{EP}foxo^EP35-147 (Junger et al., 2003, Tettweiler et al., 2005)
Cytology
Phenotypic Data
Phenotypic Class
	aging defective (with foxo²⁵) (Demontis and Perrimon, 2010) circadian rhythm defective (with foxo²⁵) (Zheng et al., 2007) developmental rate defective \| nutrition conditional (with foxo²⁵) (Kramer et al., 2008) immune response defective (with foxo^BG01018) (Dionne et al., 2006) oxidative stress response defective (with foxo²⁵) (Zheng et al., 2007) short lived (with foxo²⁵) (Sun et al., 2012) short lived \| nutrition conditional (with foxo²⁵) (Kramer et al., 2008) small body (with foxo²⁵) (Kramer et al., 2008) stress response defective (with foxo²⁵) (Tettweiler et al., 2005) viable (Junger et al., 2003)
Phenotype Manifest In
	embryonic/larval neuromuscular junction (Nechipurenko and Broihier, 2012) microtubule (Nechipurenko and Broihier, 2012) muscle cell (with foxo²⁵) (Demontis and Perrimon, 2010) synaptic vesicle (Nechipurenko and Broihier, 2012) type I bouton \| supernumerary (Nechipurenko and Broihier, 2012) wing (Junger et al., 2003)
Detailed Description
	Statement Reference foxo[21] mutant embryos do not exhibit aberrant cell fate specification or axon guidance defects. foxo[21] 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. foxo[21] mutant neuromuscular junctions display enhanced microtubule stability compared to controls. foxo[21] mutants display impaired synaptic vesicle dynamics (assayed through FM 1-43 dye). (Nechipurenko and Broihier, 2012) foxo[21]/foxo[25] flies are short lived relative to wild-type controls, but their lifespan patterns responding to diet are similar to their wild-type controls. (Sun et al., 2012) 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 foxo[21]/Df(3R)Exel8159 flies. (Cognigni et al., 2011) foxo[21]/foxo[25] mutant animals display accelerated muscle aging manifesting in the increased accumulation of age-related protein aggregates compared with wild-type flies. (Demontis and Perrimon, 2010) foxo[21]/foxo[25] 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. (Kramer et al., 2008) Starvation-induced autophagy is strongly reduced compared to controls in foxo[21]/foxo[25] larvae. (Juhász et al., 2007) foxo[21]/foxo[25] 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. foxo[21]/foxo[25] mutant flies are hypersensitive to oxidative stress. 30 day old foxo[21]/foxo[25] mutant flies show weak rhythms simliar to those seen in response to paraquat in young flies. (Zheng et al., 2007) foxo^BG01018/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. (Dionne et al., 2006) Homozygous mutant animals do not exhibit a a detectable growth phenotype. (Colombani et al., 2005) 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. (Tettweiler et al., 2005) 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. (Junger et al., 2003)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressed by
Statement Reference foxo²⁵/foxo²¹ has stress response defective phenotype, suppressible by Scer\GAL4^Act5C.PU/Thor^Scer\UAS.cTa (Tettweiler et al., 2005)
Enhancer of
Statement Reference foxo²⁵/foxo²¹ is an enhancer of decreased cell size phenotype of chico^flp147E/chico¹ (Junger et al., 2003)
Suppressor of
Statement Reference foxo²¹/foxo[+] is a suppressor \| partially of locomotor behavior defective \| adult stage \| RU486 conditional phenotype of Scer\GAL4^{elav.Switch.PO}, for^P1.Scer\UAS (Kanao et al., 2012) foxo²¹/foxo[+] is a suppressor \| partially of short lived \| RU486 conditional phenotype of Scer\GAL4^{elav.Switch.PO}, for^P1.Scer\UAS (Kanao et al., 2012) foxo²¹/foxo[+] is a suppressor \| partially of visible phenotype of Scer\GAL4^GMR.PF/Scer\GAL4^GMR.PF, cln3^Scer\UAS.cTa (Tuxworth et al., 2011) foxo²¹/foxo[+] is a suppressor of decreased cell number phenotype of chico^flp147E/chico¹ (Junger et al., 2003) foxo²¹/foxo[+] is a suppressor of long lived \| dominant phenotype of 14-3-3ε^j2B10 (Nielsen et al., 2008) foxo²¹/foxo[+] is a suppressor of long lived \| dominant phenotype of puc^E69 (Wang et al., 2005) foxo²¹/foxo[+] is a suppressor of visible phenotype of chico^flp147E/chico¹ (Junger et al., 2003) foxo²¹ is a suppressor of body size defective \| recessive phenotype of 14-3-3ε^j2B10 (Nielsen et al., 2008) foxo²¹ is a suppressor of cell growth defective phenotype of Pi3K92E^{Scer\UAS.T:Hsap\MYC}, Scer\GAL4^P0206 (Colombani et al., 2005) foxo²¹ is a suppressor of decreased cell number phenotype of Pi3K92E^{Scer\UAS.T:Hsap\MYC}, Scer\GAL4^P0206 (Colombani et al., 2005) foxo²¹ is a suppressor of decreased cell size phenotype of Pi3K92E^{Scer\UAS.T:Hsap\MYC}, Scer\GAL4^P0206 (Colombani et al., 2005) foxo²¹ is a suppressor of small body phenotype of Pi3K92E^{Scer\UAS.T:Hsap\MYC}, Scer\GAL4^P0206 (Colombani et al., 2005) foxo²⁵/foxo²¹ is a suppressor \| partially of lethal \| larval stage phenotype of Akt1¹ (Junger et al., 2003) foxo²⁵/foxo²¹ is a suppressor \| partially of small body phenotype of chico^flp147E/chico¹ (Junger et al., 2003) foxo²⁵/foxo²¹ is a suppressor of decreased cell number phenotype of chico^flp147E/chico¹ (Junger et al., 2003) foxo²⁵/foxo²¹ is a suppressor of visible phenotype of chico^flp147E/chico¹ (Junger et al., 2003)
NOT Suppressor of
Statement Reference foxo²¹/foxo[+] is a non-suppressor of decreased cell size phenotype of chico^flp147E/chico¹ (Junger et al., 2003) foxo²¹/foxo[+] is a non-suppressor of long lived phenotype of Scer\GAL4^Mhc.PW, Thor^LL.Scer\UAS (Demontis and Perrimon, 2010)
Other
Statement Reference Crtc^25-3, foxo²¹, foxo²⁵ has lethal phenotype (Wang et al., 2008)
Phenotype Manifest In
Suppressed by
Statement Reference foxo²¹ has embryonic/larval neuromuscular junction phenotype, suppressible by futsch^K68/futsch[+] (Nechipurenko and Broihier, 2012) foxo²¹ has microtubule phenotype, suppressible by futsch^K68/futsch[+] (Nechipurenko and Broihier, 2012) foxo²¹ has microtubule phenotype, suppressible by futsch^N94/futsch[+] (Nechipurenko and Broihier, 2012) foxo²¹ has synaptic vesicle phenotype, suppressible by futsch^K68/futsch[+] (Nechipurenko and Broihier, 2012) foxo²¹ has type I bouton \| supernumerary phenotype, suppressible by futsch^K68/futsch[+] (Nechipurenko and Broihier, 2012)
Enhancer of
Statement Reference foxo²⁵/foxo²¹ is an enhancer of ommatidium phenotype of chico^flp147E/chico¹ (Junger et al., 2003)
Suppressor of
Statement Reference foxo²¹/foxo[+] is a suppressor \| partially of eye phenotype of Scer\GAL4^GMR.PF/Scer\GAL4^GMR.PF, cln3^Scer\UAS.cTa (Tuxworth et al., 2011) foxo²¹/foxo[+] is a suppressor \| partially of eye phenotype of Scer\GAL4^sev.EP, hep^Act.Scer\UAS (Wang et al., 2005) foxo²¹/foxo[+] is a suppressor of ommatidium phenotype of chico^flp147E/chico¹ (Junger et al., 2003) foxo²¹/foxo[+] is a suppressor of wing phenotype of chico^flp147E/chico¹ (Junger et al., 2003) foxo²⁵/foxo²¹ is a suppressor of ommatidium phenotype of chico^flp147E/chico¹ (Junger et al., 2003) foxo²⁵/foxo²¹ is a suppressor of wing phenotype of chico^flp147E/chico¹ (Junger et al., 2003)
NOT Suppressor of
Statement Reference foxo²¹/foxo[+] is a non-suppressor of ommatidium phenotype of chico^flp147E/chico¹ (Junger et al., 2003) foxo²⁵/foxo²¹ is a non-suppressor of eye phenotype of Scer\GAL4^GMR.PF, Crtc^Scer\UAS.cWa (Wang et al., 2008)
Additional Comments
Genetic Interactions
Statement Reference The defect in climbing ability and reduction in lifespan seen in flies expressing for[P1.Scer\UAS] under the control of Scer\GAL4[elav.Switch.PO] in the presence of RU486 is partially suppressed by foxo[21]/+. (Kanao et al., 2012) A futsch[K68]/+ background suppresses the increase in type 1b bouton area observed in foxo[21] homozygotes. Furthermore, this background dominantly suppresses the elevated number of microtubule loops present in foxo[21] mutants. A futsch[N94] background dominantly suppresses the elevated number of microtubule loops present in foxo[21] mutants. A futsch[K68]/+ background suppresses the FM 1-43 loading defects found in foxo[21] mutant synapses. (Nechipurenko and Broihier, 2012) foxo[21] does not rescue the reduced body weight of Lst8[1] flies. (Wang et al., 2012) The eye phenotype resulting from the overexpression of cln3[Scer\UAS.cTa] under the control of Scer\GAL4[GMR.PF] is partially suppressed by foxo[21]/+. (Tuxworth et al., 2011) Lipid levels are completely restored in Sik3[48] ; foxo[21]/foxo[25] double mutant flies. (Wang et al., 2011) Overexpression of Thor[LL.Scer\UAS] under the control of Scer\GAL4[Mhc.PW] in a heterozygous foxo[21] mutant genetic background is sufficient to significantly extend longevity compared with wild type by increasing the median and maximum life span of flies. (Demontis and Perrimon, 2010) The 'food-leaving' behaviour of for[R], foxo[21] flies is not significantly different from for[R] flies. (Kent et al., 2009) The lifespan of 14-3-3ε[j2B10]/+, foxo[21]/+ double heterozygous flies is similar to wild-type levels. (Nielsen et al., 2008) Removal of both copies of foxo (foxo[25]/foxo[21]) is lethal in TORC[25-3] homozygotes. TORC[Scer\UAS.cWa] over-expressing flies (driven by Scer\GAL4[GMR.PF]) in which foxo is reduced or eliminated though a foxo[25]/foxo[21] background still exhibit a rough eye phenotype. (Wang et al., 2008) Ectopic expression of Thor^Scer\UAS.cTa, under the control of Scer\GAL4^Act5C 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). (Tettweiler et al., 2005) The increase in average and maximum lifespan seen in puc^E69/+ adults is dominantly suppressed by foxo²¹. (Wang et al., 2005)
Xenogenetic Interactions
Statement Reference
Complementation & Rescue Data
Rescued by	foxo²⁵/foxo²¹ is rescued by foxo^Scer\UAS.cFa/Scer\GAL4^Lk6-DJ634 (Zheng et al., 2007) foxo²⁵/foxo²¹ is rescued by foxo^T:SV5\V5 (Zheng et al., 2007) foxo²⁵/foxo²¹ is rescued by Scer\GAL4^Lk6-DJ634/foxo^{+t4.6.Scer\UAS.T:SV5\V5} (Zheng et al., 2007)
Not rescued by	foxo²⁵/foxo²¹ is not rescued by foxo^{+t4.6.Scer\UAS.T:SV5\V5}/Scer\GAL4^P2.4.Pdf (Zheng et al., 2007) foxo²⁵/foxo²¹ is not rescued by foxo^Scer\UAS.cFa/Scer\GAL4^P2.4.Pdf (Zheng et al., 2007) foxo²⁵/foxo²¹ is not rescued by foxo^T:SV5\V5 (Zheng et al., 2007)
Comments	Expression of foxo[T:SV5\V5] rescues the circadian arrhythmia seen in foxo[21]/foxo[25] mutants. Phototaxis is not affected by paraquat treatment in these mutants. Expression of foxo[Scer\UAS.cFa] under the control of Scer\GAL4[Lk6-DJ634] rescues the circadian arrhythmia seen in foxo[21]/foxo[25] mutants. Phototaxis is not affected by paraquat treatment in these mutants. (Zheng et al., 2007)
Stocks ( 0 )

Notes on Origin
Discoverer

External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 10 )
Reported As
Symbol Synonym	dfoxo21 (Nielsen et al., 2008) dfoxo21a (Slack et al., 2010) dFOXO²¹ (Puig and Tjian, 2005, Colombani et al., 2005, Junger et al., 2003, Vihervaara and Puig, 2008, Chung et al., 2010) dFoxO²¹ (Kanao et al., 2012, Kanao et al., 2010) dfoxo²¹ (Buch et al., 2008, Nielsen et al., 2008, Sun et al., 2012) dFoxo^Rw21 (Slaidina et al., 2009) foxo21 (Zid et al., 2009) FOXO²¹ (Teleman et al., 2005, Wang et al., 2011, Francis et al., 2010) foxo²¹ (Dionne et al., 2006, Wang et al., 2012, Nechipurenko and Broihier, 2012, Wang et al., 2008, Xu et al., 2012, Becker et al., 2010, Cognigni et al., 2011, Kent et al., 2009, Demontis and Perrimon, 2010, Tuxworth et al., 2011, Kramer et al., 2008, Zheng et al., 2007, Slack et al., 2011) Foxo²¹ (Juhász et al., 2007)
Name Synonym
Secondary FlyBase IDs

References ( 33 )

Generate a list of	All references relating to this allele ( 33 )

List References by type	Research paper ( 33 )
Recent research papers ( 9 )
	Kanao et al., 2012, PLoS ONE 7(2): e30958 The Nitric Oxide-Cyclic GMP Pathway Regulates FoxO and Alters Dopaminergic Neuron Survival in Drosophila. [FBrf0217639] Nechipurenko and Broihier, 2012, J. Cell Biol. 196(3): 345--362 FoxO limits microtubule stability and is itself negatively regulated by microtubule disruption. [FBrf0217391] Sun et al., 2012, Aging Cell 11(5): 783--793 Nutrient-dependent requirement for SOD1 in lifespan extension by protein restriction in Drosophila melanogaster. [FBrf0219634] Wang et al., 2012, Mol. Cell. Biol. 32(12): 2203--2213 LST8 Regulates Cell Growth via Target-of-Rapamycin Complex 2 (TORC2). [FBrf0218417] Xu et al., 2012, PLoS Genet. 8(1): e1002478 Insulin Signaling Regulates Fatty Acid Catabolism at the Level of CoA Activation. [FBrf0217254] Cognigni et al., 2011, Cell Metab. 13(1): 92--104 Enteric neurons and systemic signals couple nutritional and reproductive status with intestinal homeostasis. [FBrf0212594] Slack et al., 2011, Aging Cell 10(5): 735--748 dFOXO-independent effects of reduced insulin-like signaling in Drosophila. [FBrf0215229] Tuxworth et al., 2011, Hum. Mol. Genet. 20(10): 2037--2047 The Batten disease gene CLN3 is required for the response to oxidative stress. [FBrf0213533] Wang et al., 2011, Cell 145(4): 596--606 A hormone-dependent module regulating energy balance. [FBrf0213699] Show all research papers ...

Allele Dmel\foxo21

Allele Dmel\foxo²¹