Allele Dmel\Thor^LL.Scer\UAS

General Information
Symbol	Dmel\Thor^LL.Scer\UAS	Species	D. melanogaster
Name		FlyBase ID	FBal0147362
Feature type	allele	Associated gene	Dmel\Thor

Allele class
Mutagen	in vitro construct - regulatory fusion, in vitro construct - amino acid replacement
Recent Updates
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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
Mutagen	in vitro construct - amino acid replacement (Miron et al., 2001) in vitro construct - regulatory fusion (Miron et al., 2001)
Mutations Mapped to the Genome

Type Location Additional Notes References
Associated Sequence Data
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name

UniProtKB/Swiss-Prot
UniProtKB/TrEMBL

Progenitor genotype
Nature of the lesion	Statement Reference Construct: Amino acid replacement: M59L. Amino acid replacement: K60L. Scer\UAS regulatory sequences drive expression of a mutated form of Thor. (Miron et al., 2001)
Carried in construct	P{UAS-Thor.LL} (Roy et al., 2004, Miron et al., 2001, Zid et al., 2009, Lee et al., 2010, Gehrke et al., 2010, Demontis and Perrimon, 2010)
Cytology
Phenotypic Data
Phenotypic Class
	aging defective, with Scer\GAL4^arm.PS (Zid et al., 2009) aging defective, with Scer\GAL4^Mhc.PW (Demontis and Perrimon, 2010) cell size defective, with Scer\GAL4^Act5C.PP (Roy et al., 2004) decreased cell number, with Scer\GAL4^Bx-MS1096 (Miron et al., 2001) decreased cell number \| somatic clone, with Scer\GAL4^Act5C.PP (Miron et al., 2001) decreased cell size \| somatic clone, with Scer\GAL4^Act5C.PP (Miron et al., 2001) feeding behavior defective, with Scer\GAL4^Mhc.PW (Demontis and Perrimon, 2010) long lived, with Scer\GAL4^Mhc.PW (Demontis and Perrimon, 2010) stress response defective, with Scer\GAL4^arm.PS (Zid et al., 2009) visible, with Scer\GAL4^Bx-MS1096 (Roy et al., 2004) visible, with Scer\GAL4^dpp.blk1 (Miron et al., 2001)
Phenotype Manifest In
	1st posterior cell, with Scer\GAL4^dpp.blk1 (Miron et al., 2001) abdominal adult fat mass, with Scer\GAL4^Mhc.PW (Demontis and Perrimon, 2010) adult brain, with Scer\GAL4^Mhc.PW (Demontis and Perrimon, 2010) embryonic/larval fat body, with Scer\GAL4^Act5C.PP (Roy et al., 2004) muscle cell, with Scer\GAL4^Mhc.PW (Demontis and Perrimon, 2010) retina, with Scer\GAL4^Mhc.PW (Demontis and Perrimon, 2010) wing, with Scer\GAL4^Bx-MS1096 (Roy et al., 2004, Miron et al., 2001) wing disc, with Scer\GAL4^Bx-MS1096 (Roy et al., 2004, Miron et al., 2001) wing disc \| somatic clone, with Scer\GAL4^Act5C.PP (Miron et al., 2001)
Detailed Description
	Statement Reference Overexpression of Thor[LL.Scer\UAS] in muscles under the control of Scer\GAL4[Mhc.PW] significantly preserves muscle protein homeostasis, while the muscles of wild-type animals display increased accumulation of protein aggregates. Compared to syngenic controls, the age-related accumulation of protein aggregates in retinas, brains and the peripheral fat body of the abdomen is also decreased in flies overexpressing foxo[Scer\UAS.cFa] under the control of Scer\GAL4[Mhc.PW]. Muscle functionality gradually decreases in wild-type aging flies, resulting in impaired climbing and flight ability. Overexpression of Thor[LL.Scer\UAS] under the control of Scer\GAL4[Mhc.PW] significantly preserves muscle strength during aging. Overexpression of Thor[LL.Scer\UAS] under the control of Scer\GAL4[Mhc.PW] in muscles is sufficient to significantly extend longevity compared with wild type by increasing the median and maximum life span of flies. Food intake of flies is decreased in response to overexpression of Thor[LL.Scer\UAS] in muscles via Scer\GAL4[Mhc.PW]. The body weight of adult flies overexpressing Thor[LL.Scer\UAS] under the control of Scer\GAL4[Mhc.PW] does not significantly differ from that of syngenic controls. There is a significant decrease in the hemolymph glucose concentration compared with syngenic control in flies overexpressing Thor[LL.Scer\UAS] under the control of Scer\GAL4[Mhc.PW] (Demontis and Perrimon, 2010) Overexpression of Thor[LL.Scer\UAS] under the control of Scer\GAL4[arm.PS] extends the mean life-span of females by 14% on rich food, but does not seem to affect males. In contrast, under dietary restriction, there is no lifespan extension, beyond the effect of dietary restriction alone. (Zid et al., 2009) When expression is driven in the wing, by Scer\GAL4^Bx-MS1096, wing size is reduced, though pattern is unaffected. The effect on size is evident in the wing disc. The reduction in size is caused by reduction in cell number. When expression is driven in the eye disc, via Scer\GAL4^GMR.PF, the resulting eyes, though normally patterned, have ommatidia reduced in size (not number) compared to those of control eyes. When expression is driven by Scer\GAL4^Act5C.PP, in clones in the larval fat body, the size of the fat body cells is reduced. (Roy et al., 2004) Expression of Thor^LL.Scer\UAS under the control of Scer\GAL4^Bx-MS1096 using the P{UAS-Thor.LL}w transgene causes a marked reduction in wing size (11.2 +/- 3.4%) without affecting cell number. Wing discs in these animals are indistinguishable from control discs. Expression of Thor^LL.Scer\UAS under the control of Scer\GAL4^Bx-MS1096 using the P{UAS-Thor.LL}s transgene causes a marked reduction in wing size (37.1 +/- 2.7%) which is partly due to a decrease in cell number (19.0 +/- 4.3%). Wing discs in these animals are 52% smaller than normal and contain many apoptotic cells. The flies take 1-2 days longer to eclose than normal. Clones in the wing disc expressing Thor^LL.Scer\UAS under the control of Scer\GAL4^Act5C.PP using the P{UAS-Thor.LL}w transgene have fewer cells than wild-type clones. Few clones in the wing disc expressing Thor^LL.Scer\UAS under the control of Scer\GAL4^Act5C.PP using the P{UAS-Thor.LL}s transgene are recovered and they usually contain 1-2 cells. Clones in the wing disc expressing Thor^LL.Scer\UAS under the control of Scer\GAL4^Act5C.PP are smaller in size than wild type. Clones in the fat body expressing Thor^LL.Scer\UAS under the control of Scer\GAL4^Act5C.PP using the P{UAS-Thor.LL}s transgene are 45-70% smaller than neighbouring wild-type cells. Clones in the fat body expressing Thor^LL.Scer\UAS under the control of Scer\GAL4^Act5C.PP using the P{UAS-Thor.LL}s transgene are recovered in the posterior of the eye disc but are absent from the anterior of the eye disc and the antennal disc. Expression of Thor^LL.Scer\UAS under the control of Scer\GAL4^dpp.blk1 using the P{UAS-Thor.LL}s transgene results in reduction in size of the region encompassed by wing veins 3 and 4, the anterior crossvein and the wing margin. (Miron et al., 2001)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
NOT suppressed by
Statement Reference Scer\GAL4^Mhc.PW, Thor^LL.Scer\UAS has long lived phenotype, non-suppressible by foxo²¹/foxo[+] (Demontis and Perrimon, 2010)
Phenotype Manifest In
Suppressed by
Statement Reference Scer\GAL4^Bx-MS1096, Thor^LL.Scer\UAS has wing disc phenotype, suppressible \| partially by BacA\p35^Scer\UAS.cHa, Scer\GAL4^Bx-MS1096 (Miron et al., 2001)
Additional Comments
Genetic Interactions
Statement Reference 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) Co-expression of BacA\p35^Scer\UAS.cHa partially rescues the reduced size of wing discs in animals expressing Thor^LL.Scer\UAS under the control of Scer\GAL4^Bx-MS1096 using the P{UAS-Thor.LL}s transgene. The number of cells in clones in the wing disc expressing Thor^LL.Scer\UAS under the control of Scer\GAL4^Act5C.PP using the P{UAS-Thor.LL}w is not affected by co-expression of BacA\p35^Scer\UAS.cHa. Co-expression of BacA\p35^Scer\UAS.cHa greatly increases the number of clones recovered in the wing disc expressing Thor^LL.Scer\UAS under the control of Scer\GAL4^Act5C.PP using the P{UAS-Thor.LL}s transgene, but only marginally increases the number of cells per clone. The region of the wing encompassed by wing veins 3 and 4, the anterior crossvein and the wing margin is reduced in size when Thor^LL.Scer\UAS is expressed under the control of Scer\GAL4^dpp.blk1 using the P{UAS-Thor.LL}s transgene in a Df(2L)Pi3K21B-A/+; P{U2af38.gR10} background. (Miron et al., 2001)
Xenogenetic Interactions
Statement Reference
Complementation & Rescue Data
Comments
Stocks ( 2 )
Bloomington	8651 w¹¹¹⁸; P{UAS-p35.H}BH1; P{UAS-Thor.LL}s 24854 w^*; P{UAS-Thor.LL}s/TM6C, cu¹ Sb¹
Notes on Origin
Discoverer

External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 1 )
Reported As
Symbol Synonym	Thor^LL.Scer\UAS
Name Synonym
Secondary FlyBase IDs

References ( 6 )
Research paper	Demontis and Perrimon, 2010, Cell 143(5): 813--825 FOXO/4E-BP Signaling in Drosophila Muscles Regulates Organism-wide Proteostasis during Aging. [FBrf0212347] Gehrke et al., 2010, Nature 466(7306): 637--641 Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. [FBrf0211387] Lee et al., 2010, Science 327(5970): 1223--1228 Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. [FBrf0210161] Zid et al., 2009, Cell 139(1): 149--160 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. [FBrf0209084] Roy et al., 2004, Mol. Cell. Biol. 24(3): 1143--1154 The Drosophila poly(A) binding protein-interacting protein, dPaip2, is a novel effector of cell growth. [FBrf0167891] Miron et al., 2001, Nat. Cell Biol. 3(6): 596--601 The translational inhibitor 4E-BP is an effector of PI(3)K/Akt signalling and cell growth in Drosophila. [FBrf0137059]

Allele Dmel\ThorLL.Scer\UAS

Allele Dmel\Thor^LL.Scer\UAS