FlyBase Allele Report: Dmel\Sirt1[EP2300]

General Information

Symbol

Dmel\Sirt1^EP2300

Species

D. melanogaster

Name

FlyBase ID

FBal0119385

Feature type

allele

Associated gene

Dmel\Sirt1

Associated Insertion(s)

P{EP}Sirt1^EP2300

Carried in Construct

Also Known As

dSir2^EP2300, EP(2)2300, Sir2^EP2300

Key Links

Genomic Maps

JBrowse

Allele class

Mutagen

P-element activity

Nature of the Allele

Allele class

Mutagen

P-element activity

(Rosenberg and Parkhurst, 2002, Gene Disruption Project members, 2001-, Fernandez-Funez et al., 2000, FlyBase, 1996-)

Progenitor genotype

Associated Insertion(s)

P{EP}Sirt1^EP2300

Cytology

Description

P{EP} insertion approximately 400bp upstream of Sir2. The P{EP} insertion is in the correct orientation to drive overexpression of Sir2 from the Scer\UAS regulatory sequences within the P{EP} element.

(Rosenberg and Parkhurst, 2002)

The P{EP} insertion is 427bp upstream of the putative ATG start codon in the same orientation to the transcription unit.

(Fernandez-Funez et al., 2000)

The P{EP}Sir2^EP2300 insertion maps within both Sir2 and DnaJ-H (overlapping genes on opposite strands).

(FlyBase, 1996-)

Allele components

Component

Use(s)

Inserted element

P{EP}

misexpression element

Regulatory region(s)

UAS

binary expression system - regulatory region

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

transposable_element_insertion_site

2L:13,165,561..13,165,561 [+]

(Wen et al., 2019, Horvath et al., 2016, Sanhueza et al., 2015, Burnett et al., 2011, Branco et al., 2008, Griswold et al., 2008, Pallos et al., 2008, Furuyama et al., 2004, Ghosh and Feany, 2004, Rogina and Helfand, 2004, Rosenberg and Parkhurst, 2002, Gene Disruption Project members, 2001-, Fernandez-Funez et al., 2000, FlyBase, 1996-)

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 ( 0 )

Disease

Evidence

References

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

ameliorates Parkinson's disease

modeled by Pink1^B9

(Koh et al., 2012)

exacerbates autosomal dominant cerebellar ataxia

modeled by Hsap\ATXN1^82.UAS

(Ghosh and Feany, 2004)

modeled by Hsap\ATXN1^82Q.UAS

(Fernandez-Funez et al., 2000)

modeled by Hsap\ATXN1^30Q.UAS

(Fernandez-Funez et al., 2000)

exacerbates Huntington's disease

modeled by Hsap\HTT^{128Q.1-336.UAS}

(Branco et al., 2008)

exacerbates olivopontocerebellar atrophy

modeled by Hsap\ATXN1^82Q.UAS

(Branco et al., 2008)

ameliorates amyotrophic lateral sclerosis type 8

modeled by Vap33^{P58S.UAS.Tag:FLAG}

(Sanhueza et al., 2015)

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

Disease-implicated variant(s)

Phenotypic Data

Phenotypic Class

abnormal gravitaxis | adult stage, with Scer\GAL4^Hand.PU

(Wen et al., 2019)

long lived, with Scer\GAL4^arm.PS

(Rogina and Helfand, 2004)

long lived, with Scer\GAL4^elav-C155

(Pallos et al., 2008, Rogina and Helfand, 2004)

long lived, with Scer\GAL4^Hand.PU

(Wen et al., 2019)

long lived, with Scer\GAL4^αTub84B.PL

(Rogina and Helfand, 2004)

long lived | RU486 conditional, with Scer\GAL4^{elav.Switch.PO}

(Rogina and Helfand, 2004)

viable

(Furuyama et al., 2004)

visible | adult stage, with Scer\GAL4^sca.PU

(Horvath et al., 2016)

Phenotype Manifest In

adult heart, with Scer\GAL4^Hand.PU

(Wen et al., 2019)

scutellar bristle, with Scer\GAL4^sca.PU

(Horvath et al., 2016)

Detailed Description

Statement

Reference

Expression of Sirt1^EP2300 under the control of Scer\GAL4^Hand.PU leads to significantly increased heart period, diastolic period, and fractional shortening whereas it leads to significantly decreased diastolic dysfunction index while it does not lead to any changes in systolic periods, systolic diameter or diastolic diameter when compared to control adults. Exercise training significantly enhances these hearth function phenotypes, except the systolic period phenotype.

Expression of Sirt1^EP2300 under the control of Scer\GAL4^Hand.PU significantly increases the climbing index of 5-week-old flies (but not of 1-, 3- or 7-week-old flies) compared to controls. Exercise increases the climbing index of 5- and 7-week-old (but not of 1-week-old or 3-week-old) flies that express Sirt1^EP2300 under the control of Scer\GAL4^Hand.PU and it extends the lifespan of flies that express Sirt1^EP2300 under the control of Scer\GAL4^Hand.PU compared to control adults.

(Wen et al., 2019)

Expression of Sirt1^EP2300 under the control of Scer\GAL4^sca.PU leads to a partial loss of the scutellar bristles.

(Horvath et al., 2016)

Flies expressing Sir2^EP2300 under the control of Scer\GAL4^tub.PU show no increase in lifespan compared to the control carrying the Scer\GAL4^tub.PU driver alone.

(Burnett et al., 2011)

Overexpression of Sir2^EP2300 under the control of Scer\GAL4^elav-C155 significantly extends adult lifespan.

(Pallos et al., 2008)

Sir2^EP2300; Scer\GAL4^αTub84B.PL females live on average 57% longer than controls and have a maximal life span (mean of 10% survival) of 19% longer than controls. For males of this genotype, the equivalent figures are 32% and 14% respectively. These lifespan increases are somewhat reduced by a low calorie diet. Similar increases in lifespan are seen when Scer\GAL4^elav-C155 is used as a driver in stead of Scer\GAL4^αTub84B.PL : female average lifespan up 52% and maximal lifespan up 19%; male average lifespan up 20% and maximal lifespan up 8%. Lifespan is not further increased in these flies by a low calorie diet. When Scer\GAL4^arm.PS is used as the driver, there is only a 10-20% increase in average lifespan and no increase in maximal lifespan compared to controls. No increase in lifespan is seen when the driver is Scer\GAL4^D42. The presence of 200μM RU486 in the food of Sir2^EP2300; Scer\GAL4^{elav.Switch.PO} females increases average lifespan by 5-12% and maximal lifespan by 9-16%.

(Rogina and Helfand, 2004)

Expression of Sir2^EP2300 under the control of Scer\GAL4^GMR.PF does not result in a rough eye phenotype.

(Shulman and Feany, 2003)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhancer of

Statement

Reference

Sirt1^EP2300/Sir2[+] is an enhancer of visible | homeotic phenotype of E(z)³²/E(z)⁶¹

(Furuyama et al., 2004)

NOT Enhancer of

Statement

Reference

Sirt1^EP2300, Scer\GAL4^GMR.PF is a non-enhancer of visible phenotype of Hsap\MAPT^V337M.UAS, Scer\GAL4^GMR.PF

(Shulman and Feany, 2003)

Suppressor of

Statement

Reference

Scer\GAL4^ple.PF/Sirt1^EP2300 is a suppressor of decreased cell number | adult stage phenotype of Pink1^B9

(Koh et al., 2012)

Scer\GAL4^ple.PF, Sirt1^EP2300, foxo²¹, foxo[+] is a suppressor | partially of decreased cell number | adult stage phenotype of Pink1^B9

(Koh et al., 2012)

Sirt1^EP2300/Sir2[+] is a suppressor of long lived phenotype of HDAC1^def24

(Rogina and Helfand, 2004)

NOT Suppressor of

Statement

Reference

Sirt1^EP2300, Scer\GAL4^elav-C155 is a non-suppressor of increased mortality phenotype of Hsap\HTT^Q93.ex1.UAS, Scer\GAL4^elav-C155

(Pallos et al., 2008)

Sirt1^EP2300, Scer\GAL4^GMR.PF is a non-suppressor of visible phenotype of Hsap\MAPT^V337M.UAS, Scer\GAL4^GMR.PF

(Shulman and Feany, 2003)

Phenotype Manifest In

Enhancer of

Statement

Reference

Sirt1^EP2300, Scer\GAL4^GMR.PU is an enhancer of retina phenotype of Hsap\HTT^{128Q.1-336.UAS}, Scer\GAL4^GMR.PU

(Branco et al., 2008)

Sirt1^EP2300, Scer\GAL4^GMR.PF is an enhancer of retina phenotype of Hsap\ATXN1^82.UAS, Scer\GAL4^GMR.PF

(Ghosh and Feany, 2004)

Sirt1^EP2300, Scer\GAL4^GMR.PF is an enhancer of eye phenotype of Hsap\ATXN1^82Q.UAS, Scer\GAL4^GMR.PF

(Fernandez-Funez et al., 2000)

Sirt1^EP2300, Scer\GAL4^GMR.PF is an enhancer of retina phenotype of Hsap\ATXN1^82Q.UAS, Scer\GAL4^GMR.PF

(Fernandez-Funez et al., 2000)

NOT Enhancer of

Statement

Reference

Sirt1^EP2300, Scer\GAL4^GMR.PF is a non-enhancer of retina phenotype of Hsap\ATXN3^{tr.Q78.UAS.Tag:HA}, Scer\GAL4^GMR.PF

(Ghosh and Feany, 2004)

Sirt1^EP2300, Scer\GAL4^30Y is a non-enhancer of adult brain phenotype of Hsap\ATXN3^{tr.Q78.UAS.Tag:HA}, Scer\GAL4^30Y

(Ghosh and Feany, 2004)

Sirt1^EP2300, Scer\GAL4^ChAT.7.4 is a non-enhancer of adult brain phenotype of Hsap\ATXN1^82.UAS, Scer\GAL4^ChAT.7.4

(Ghosh and Feany, 2004)

Sirt1^EP2300/Scer\GAL4^GMR.PF is a non-enhancer of retina phenotype of Scer\GAL4^GMR.PF, Zzzz\CAG^{127Q.UAS.Tag:HA}

(Ghosh and Feany, 2004)

Sirt1^EP2300, Scer\GAL4^GMR.PF is a non-enhancer of eye phenotype of Hsap\MAPT^V337M.UAS, Scer\GAL4^GMR.PF

(Shulman and Feany, 2003)

Suppressor of

Statement

Reference

Scer\GAL4^ple.PF/Sirt1^EP2300 is a suppressor of mitochondrion | adult stage phenotype of Pink1^B9

(Koh et al., 2012)

Scer\GAL4^ple.PF, Sirt1^EP2300, foxo²¹, foxo[+] is a suppressor | partially of dorso-lateral dopaminergic neuron phenotype of Pink1^B9

(Koh et al., 2012)

Scer\GAL4^ple.PF, Sirt1^EP2300, foxo²¹, foxo[+] is a suppressor | partially of mitochondrion | adult stage phenotype of Pink1^B9

(Koh et al., 2012)

Scer\GAL4^ple.PF/Sirt1^EP2300 is a suppressor of dorso-lateral dopaminergic neuron phenotype of Pink1^B9

(Koh et al., 2012)

Sirt1^EP2300, Scer\GAL4^GMR.PU is a suppressor of retina phenotype of Hsap\ATXN1^82Q.UAS, Scer\GAL4^GMR.PU

(Branco et al., 2008)

NOT Suppressor of

Statement

Reference

Sirt1^EP2300, Scer\GAL4^30Y is a non-suppressor of adult brain phenotype of Hsap\ATXN3^{tr.Q78.UAS.Tag:HA}, Scer\GAL4^30Y

(Ghosh and Feany, 2004)

Sirt1^EP2300, Scer\GAL4^ChAT.7.4 is a non-suppressor of adult brain phenotype of Hsap\ATXN1^82.UAS, Scer\GAL4^ChAT.7.4

(Ghosh and Feany, 2004)

Sirt1^EP2300/Scer\GAL4^GMR.PF is a non-suppressor of retina phenotype of Scer\GAL4^GMR.PF, Zzzz\CAG^{127Q.UAS.Tag:HA}

(Ghosh and Feany, 2004)

Sirt1^EP2300, Scer\GAL4^GMR.PF is a non-suppressor of retina phenotype of Hsap\ATXN3^{tr.Q78.UAS.Tag:HA}, Scer\GAL4^GMR.PF

(Ghosh and Feany, 2004)

Sirt1^EP2300, Scer\GAL4^GMR.PF is a non-suppressor of eye phenotype of Hsap\MAPT^V337M.UAS, Scer\GAL4^GMR.PF

(Shulman and Feany, 2003)

Additional Comments

Genetic Interactions

Statement

Reference

Expression of Sirt1^EP2300 driven by Scer\GAL4^ple.PF suppresses the enlarged mitochondria in dopaminergic neurons and dopaminergic neuron loss (DL1 cluster) seen in Pink1^B9/Y flies; additional presence of foxo²¹/+ partially suppresses the suppressive effect of Sirt1^EP2300 driven by Scer\GAL4^ple.PF on these phenotypes in Pink1^B9/Y flies.

(Koh et al., 2012)

Expression of P{EP}Sir2^EP2300 under the control of Scer\GAL4^GMR.PU (which results in the simultaneous over-expression of both Sir2 and DnaJ-H) has no effect on eye morphology.

(Griswold et al., 2008)

The increased average lifespan of HDAC1^def24 homozygous flies is suppressed by Sirt1^EP2300/+.

(Rogina and Helfand, 2004)

Xenogenetic Interactions

Statement

Reference

Expression of Sir2^EP2300 enhances the retinal phenotype seen when Hsap\HTT^{128Q.1-336.Scer\UAS} is expressed under the control of Scer\GAL4^GMR.PU.

Expression of Sir2^EP2300 enhances the retinal phenotype seen when Hsap\ATXN1^82Q.Scer\UAS is expressed under the control of Scer\GAL4^GMR.PU.

(Branco et al., 2008)

Overexpression of Sir2^EP2300 does not reduce the lethality associated with expression of Hsap\HTT^{Q93.ex1p.Scer\UAS} (when both are driven by Scer\GAL4^elav-C155). Addition of resveratrol to food fed to these 'double mutant' flies rescues the neuronal degeneration phenotype found in these flies, in a dose-dependent manner.

(Pallos et al., 2008)

The rough eye phenotype caused by expression of Hsap\MAPT^{V337M.Scer\UAS} under the control of Scer\GAL4^GMR.PF is not modified if the flies are also carrying Sir2^EP2300.

(Shulman and Feany, 2003)

Complementation and Rescue Data

Comments

Images (0)

Mutant

Wild-type

Stocks (1)

Bloomington

24859

w¹¹¹⁸; P{EP}Sirt1^EP2300 DnaJ-H^EP2300/CyO

Notes on Origin

Discoverer

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (4)

Reported As

Symbol Synonym

EP(2)2300

(Shulman and Feany, 2003)

Sir2^EP2300

(Banerjee et al., 2012, Koh et al., 2012)

Sirt1^EP2300

(Banerjee et al., 2017, Horvath et al., 2016)

dSir2^EP2300

(Whitaker et al., 2013, Burnett et al., 2011, Kanao et al., 2010, Rogina and Helfand, 2004)

Name Synonyms

Secondary FlyBase IDs

References (20)

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