FlyBase Allele Report: Dmel\Atpα[DTS1]

General Information

Symbol

Dmel\Atpα^DTS1

Species

D. melanogaster

Name

FlyBase ID

FBal0188150

Feature type

allele

Associated gene

Dmel\Atpα

Associated Insertion(s)

Carried in Construct

Also Known As

ATPalpha^DTS1

Key Links

Genomic Maps

JBrowse

Allele class

heat sensitive gain of function allele

Mutagen

ethyl methanesulfonate

Nature of the Allele

Allele class

heat sensitive gain of function allele

(Palladino et al., 2003)

Mutagen

ethyl methanesulfonate

(Palladino et al., 2003)

Progenitor genotype

Cytology

Description

Atpα protein expression levels are normal in heterozygotes.

(Ashmore et al., 2009)

Amino acid replacement: E982K.

(Palladino et al., 2003)

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

point_mutation

3R:20,973,866..20,973,866 [+]

Nucleotide change:

G20973866A

Amino acid change:

Reported amino acid change:

E982K

Comment:

Site of nucleotide substitution in mutant inferred by FlyBase based on reported amino acid change.

(Palladino et al., 2003)

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 nervous system disease

CEA

(Talsma et al., 2014, Fergestad et al., 2006, Palladino et al., 2003)

model of epilepsy

CEA

(Fergestad et al., 2006)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of nervous system disease

is exacerbated by CG5888^MB00188

(Talsma et al., 2014)

is exacerbated by Cyt-c1L^G9163

(Talsma et al., 2014)

is exacerbated by Dyrk2¹

(Talsma et al., 2014)

is exacerbated by Gαo^MB04922

(Talsma et al., 2014)

is exacerbated by Glt^EY22126

(Talsma et al., 2014)

is exacerbated by Nadk1b^MB05931

(Talsma et al., 2014)

is exacerbated by RpL19^k03704

(Talsma et al., 2014)

is exacerbated by SLO2^MB04544

(Talsma et al., 2014)

is exacerbated by aly¹

(Talsma et al., 2014)

is exacerbated by galectin^DG25505

(Talsma et al., 2014)

is ameliorated by ppk11^MB02012

(Talsma et al., 2014)

is exacerbated by rasp^m47

(Talsma et al., 2014)

is exacerbated by scramb2^EY01180

(Talsma et al., 2014)

exacerbates epilepsy

modeled by eag¹

(Fergestad et al., 2006)

modeled by Sh¹⁴

(Fergestad et al., 2006)

modeled by Sh¹⁴, eag¹

(Fergestad et al., 2006)

modeled by sei¹

(Fergestad et al., 2006)

modeled by para^ts1

(Fergestad et al., 2006)

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

Disease-implicated variant(s)

Phenotypic Data

Phenotypic Class

abnormal locomotor behavior | adult stage

(Palladino et al., 2003)

abnormal neuroanatomy | adult stage | dominant

(Palladino et al., 2003)

abnormal neurophysiology | heat sensitive

(Palladino et al., 2003)

bang sensitive (with Atpα²²⁰⁶)

(Palladino et al., 2003)

bang sensitive | dominant | heat sensitive

(Palladino et al., 2003)

lethal - all die during embryonic stage (with Atpα^DTS1R1)

(Palladino et al., 2003)

lethal - all die during embryonic stage (with Atpα^DTS1R2)

(Palladino et al., 2003)

lethal - all die during embryonic stage (with Atpα^DTS2R1)

(Palladino et al., 2003)

lethal - all die during embryonic stage (with Atpα^DTS2R2)

(Palladino et al., 2003)

lethal - all die during embryonic stage (with Atpα^DTS2R3)

(Palladino et al., 2003)

lethal - all die during embryonic stage (with Atpα^H64)

(Palladino et al., 2003)

lethal - all die during embryonic stage | recessive

(Palladino et al., 2003)

paralytic | dominant | heat sensitive

(Palladino et al., 2003)

paralytic | heat sensitive

(Fergestad et al., 2006)

paralytic | heat sensitive (with Atpα^01453a)

(Palladino et al., 2003)

paralytic | heat sensitive (with Atpα²²⁰⁶)

(Palladino et al., 2003)

paralytic | heat sensitive (with Atpα^DTS2)

(Palladino et al., 2003)

partially lethal - majority die (with Atpα^01453a)

(Palladino et al., 2003)

partially lethal - majority die (with Atpα^DTS2)

(Palladino et al., 2003)

short lived

(Palladino et al., 2003)

short lived | dominant

(Fergestad et al., 2006)

some die during embryonic stage (with Atpα^DTS1R1)

(Palladino et al., 2003)

some die during embryonic stage (with Atpα^DTS1R2)

(Palladino et al., 2003)

some die during embryonic stage (with Atpα^DTS2R1)

(Palladino et al., 2003)

some die during embryonic stage (with Atpα^DTS2R2)

(Palladino et al., 2003)

some die during embryonic stage (with Atpα^DTS2R3)

(Palladino et al., 2003)

some die during embryonic stage (with Atpα^H64)

(Palladino et al., 2003)

some die during embryonic stage | recessive

(Palladino et al., 2003)

Phenotype Manifest In

adult brain

(Palladino et al., 2003)

adult ventral nerve cord

(Palladino et al., 2003)

dorsal longitudinal indirect flight muscle cell

(Palladino et al., 2003)

Detailed Description

Statement

Reference

Heterozygous mutants have a significantly lower respiration (metabolic) rate than controls.

(Ashmore et al., 2009)

Atpα^DTS1/+ flies show a significant reduction in lifespan compared to controls. Atpα^DTS1 flies become instantly paralyzed upon exposure to a 15 minute 38^oC heat shock. When returned to 22^oC, >60% never recover and survivors only begin to show movement after over an hour at the permissive temperature.

(Fergestad et al., 2006)

Atpα^DTS1/+ flies are sluggish compared to wild-type. After exposure to 37-38^oC, these mutants become paralyzed within 10-30 seconds with complete penetrance. If this restrictive temperature is maintained for 3 minutes, then flies regain the ability to stand after 1-2 minutes at the permissive temperature and can only walk after another few minutes. Wild-type flies never become paralyzed from exposure to 37-38^oC. Although Atpα^DTS1/+ flies do not show paralysis in response to mechanical shock when maintained and tested at 20-22^oC, bang-sensitive paralysis does occur when flies are tested at 20-22^oC if they have been maintained at 28^oC. This phenomenon can occur for several hours after placing in the permissive temperature and paralysis lasts around 5-30 seconds. At elevated temperatures (37^oC) continuous spiking activity is observed in thoracic readings taken from the dorsal flight muscles of Atpα^DTS1 flies, but not in those of wild-type flies. Atpα^DTS1 flies have significantly shorter lifespans than wild type and become quite sedentary as they age, with a premature loss of both walking and flight activity. In the brains of middle-aged Atpα^DTS1/+ flies, neurodegeneration is evident as the appearance of vacuolar structures throughout the central brain and optic regions. Such structures are rarely seen in wild-type flies. The phenotype is age dependent as young adults (day 2-3 after eclosion) show little neuropathology. This age-dependent neurodegeneration can also be seen in the thoracic ganglion.

(Palladino et al., 2003)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

Enhanced by

Statement

Reference

Atpα^DTS1 has short lived | dominant phenotype, enhanceable by para^ST109/para[+]

(Fergestad et al., 2006)

Atpα^DTS1 has short lived | dominant phenotype, enhanceable by para[+]/para^ts1

(Fergestad et al., 2006)

Atpα^DTS1 has short lived | dominant phenotype, enhanceable by para^ts115/para[+]

(Fergestad et al., 2006)

NOT Enhanced by

Statement

Reference

Atpα^DTS1 has short lived | dominant phenotype, non-enhanceable by Df(1)D34/+

(Fergestad et al., 2006)

Atpα^DTS1 has short lived | dominant phenotype, non-enhanceable by Sh¹⁴/Sh[+]

(Fergestad et al., 2006)

Atpα^DTS1 has short lived | dominant phenotype, non-enhanceable by Sh^{EKO.UAS.GFP(GL)}/Scer\GAL4^elav.PLu

(Fergestad et al., 2006)

Atpα^DTS1 has short lived | dominant phenotype, non-enhanceable by Scer\GAL4^hs.2sev/Sh^{EKO.UAS.GFP(GL)}

(Fergestad et al., 2006)

Atpα^DTS1 has short lived | dominant phenotype, non-enhanceable by eag[+]/eag¹

(Fergestad et al., 2006)

Atpα^DTS1 has short lived | dominant phenotype, non-enhanceable by para^lk5/para[+]

(Fergestad et al., 2006)

Atpα^DTS1 has short lived | dominant phenotype, non-enhanceable by sei¹/sei[+]

(Fergestad et al., 2006)

NOT Enhancer of

Statement

Reference

Atpα^DTS1/Atpα^DTS1 is a non-enhancer of short lived phenotype of Sh¹⁴, eag¹

(Fergestad et al., 2006)

Phenotype Manifest In

Enhanced by

Statement

Reference

Atpα^DTS1 has adult brain phenotype, enhanceable by para[+]/para^ts1

(Fergestad et al., 2006)

Enhancer of

Statement

Reference

Atpα^DTS1/Atpalpha[+] is an enhancer of adult brain phenotype of para^ts1

(Fergestad et al., 2006)

Additional Comments

Genetic Interactions

Statement

Reference

There is no additional reduction in lifespan in eag¹, Sh¹⁴; Atpα^DTS1 triple mutants compared to eag¹, Sh¹⁴ mutants. The following heterozygous mutants do not enhance the shortened lifespan of Atpα^DTS1/+ mutants: eag¹, Sh¹⁴, and sei¹. The short lived phenotype of Atpα^DTS1 heterozygotes is enhanced in para^ts1/+, para^ST109/+ and para^ts115/+ flies. In contrast, heterozygosity for either para^lk5 or Df(1)D34 does not shorten the Atpα^DTS1 life span. In addition to a shorter lifespan, para^ts1/+; Atpα^DTS1/+ double mutants show an increase in the severity of spongiform neuropathology of the brain at 16 days compared to brains from para^ts1/+ or Atpα^DTS1/+ single mutants. These double mutants show no significant change in temperature sensitivity compared to the single mutants. Like Atpα^DTS1 single mutants, para^ts1; Atpα^DTS1 mutants need several minutes to recover from a 3 minute 38^oC heat shock. There is no significant change in the lifespan of Atpα^DTS1 mutants when they express Sh^{EKO.Scer\UAS.T:Avic\GFP-GL} under the control of either Scer\GAL4^elav.PLu or Scer\GAL4^hs.2sev.