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General Information
Symbol
Dmel\sws1
Species
D. melanogaster
Name
FlyBase ID
FBal0016670
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Key Links
Allele class
Nature of the Allele
Allele class
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Nucleotide change:

C7963853A

Reported nucleotide change:

C1616A

Amino acid change:

S375term | sws-PA; S375term | sws-PC

Reported amino acid change:

S375term

Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Cytology
Nature of the lesion
Statement
Reference

The sws1 mutation produces a truncated polypeptide that terminates at residue 375, thus lacking the esterase domain.

Nucleotide substitution: C1616A.

Amino acid replacement: S375term.

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 )
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

sws1 adults show a progressive decrease in locomotion in fast phototaxis assays, and barely move by day 14, when they exhibit severe vacuolization of the deutocerebral neuropil.

sws1/sws1 1 day old adults show glial hyper-wrapping and incomplete glial wrapping of neuronal cell bodies and stunted glial processes in the medulla cortex.

sws1/sws1 flies (two days old) have a significantly reduced performance in a phototaxis assay (measuring percentage transitions towards light) compared to controls; this phenotype is progressive, with performance in 14 day old flies worse than in 2 day old flies.

sws1 mutant brains exhibit progressive neurodegeneration, with a significant increase in vacuole formation at 7, 14, and 21 days old, but not at 1 day old, as compared to wild type.

sws1 flies shortly before eclosion have normal eyes with all photoreceptors present. Whereas 14-day-old flies still have mostly intact ommatidia (occasionally one photoreceptor is lost), at 23 days the photoreceptors are either lost or show degenerative signs such as condensed cell bodies, intracellular membranous bodies or vacuoles.

sws1 flies show neurodegeneration compared to controls, with vacuoles present in the brain at 14 days of age.

sws1/+ flies do not exhibit a significant difference in performance in a phototaxis assay, as compared to controls; but both sws1/+ and sws1/sws1 flies exhibit significantly increased vacuolization in the brain as compared to wild type.

sws1 mutants at 14 days old do not display any marked defects in circadian rhythms, but do exhibit symptoms of neurodegeneration evidenced by vacuoles in the brain.

14 day old vapKS67 mutant flies show vacuoles in all parts of the brain. These increase dramatically with age.

sws1/sws1 flies show vacuolization in the neuropil.

sws1 flies exhibit vacuolisation in the neuropil (due to degeneration of neurites) and the formation of membranous glial bodies.

sws1 flies exhibit a strong glial phenotype consisting of the formation of multilayered glial wrappings and subsequent glial cell death.

Adults have vacuoles in all brain regions. This degeneration increases with age, as shown by an increased number of vacuoles and shrinking of the cell cortex. An increasing amount of cell death is also seen in the brain. Compact dark bodies are seen in the cortex, especially the lamina cortex. These structures are first seen during late pupal stages, and increase in size during aging of the adult. Approximately 10% of brain cortex neurons are enwrapped by multilayered membranes originating from nearby glia in newly eclosed flies. Membranous whorls are seen in older flies. Homozygotes adults show a significant reduction in lifespan compared to wild-type flies.

many Swiss-cheese-like holes seen in brain sections of adults (similar to phenotype observed in dying drd flies). Phenotype has become less extreme, apparently due to accumulation of modifiers (Heisenberg).

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
NOT Enhanced by
Suppressed by
Statement
Reference
NOT suppressed by
Enhancer of
Other
Phenotype Manifest In
Enhanced by
Statement
Reference
NOT Enhanced by
Statement
Reference
Suppressed by
NOT suppressed by
Enhancer of
Statement
Reference
Other
Additional Comments
Genetic Interactions
Statement
Reference

per01, sws1 double mutants at 14 days old show marked increase in neurodegeneration as measured by area and number of vacuoles in the brain as compared to sws1 single mutants.

A subset of per01, sws1 double mutants exhibit some rhythmicity (13% of flies), in contrast to per01 single mutants in which 0% of flies have circadian rhythm, and sws1 single mutants in which 97% of flies have circadian rhythm.

Expression of Appls.Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4elav-C155 fails to suppress the vacuolisation seen in the brains of sws1 mutant 14 day old males.

Expression of ApplScer\UAS.cCSa under the control of Scer\GAL4elav-C155 fails to suppress the vacuolisation seen in the brains of sws1 mutant 14 day old males.

Expression of Pka-C3Scer\UAS.cBa driven pan-neuronally by Scer\GAL4Appl.G1a enhances neuropil vacuolization in sws1/sws1 flies. Df(3L)brm11/+ partially suppresses neuropil vacuolization in the lamina cortex (but not central brain) of sws1/sws1 flies. Pka-C1C2/+ does not enhance vacuole formation in sws1/sws1 flies.

sws1/+ enhances degeneration (neuropil vacuolization) in aged male flies with expression of Pka-C3Scer\UAS.cBa driven pan-neuronally by Scer\GAL4Appl.G1a, and also results in vacuolization in aged females.

Xenogenetic Interactions
Statement
Reference

Expression of Hsap\PNPLA6Scer\UAS.cTa driven by Scer\GAL4Appl.PU significantly partially suppresses neurodegeneration (vacuoles in the brain) in 14 day old sws1 flies. Expression of Hsap\PNPLA6F1M.Scer\UAS driven by Scer\GAL4Appl.PU significantly enhances neurodegeneration sws1 flies. Expression of Hsap\PNPLA6F2M1.Scer\UAS or Hsap\PNPLA6F2M2.Scer\UAS driven by Scer\GAL4Appl.PU does not affect neurodegeneration sws1 flies.

Neuronal expression of Mmus\NTEScer\UAS.cMa, under the control of Scer\GAL4elav-C155 rescues some aspects of the neuronal degeneration, namely the vacuolisation in the neuropil.

Glial expression of Mmus\NTEScer\UAS.cMa, under the control of Scer\GAL4loco.1.3 rescues the glial phenotype.

Expression of Mmus\NTEScer\UAS.cMa in either neurons or glia (under the control of either Scer\GAL4elav-C155 or Scer\GAL4loco.1.3) restores the wild-type NTE-like activity (NTE-neuropathy target esterase).

Complementation and Rescue Data
Comments

Expression of swsScer\UAS.cMa driven by Scer\GAL4loco.PU partially restores glial wrapping of neuronal cell bodies in the medulla cortex and neurites in the medulla neuropil in sws1/sws1 flies, though some vacuoles are still present (glial hyper-wrapping no longer occurs).

Scer\GAL4elav.PU>swsScer\UAS.cMa flies still show incomplete glial wrapping in the medulla, though glial sheaths are present in some neuronal cell bodies in the medulla cortex and neurites in the medulla neuropil in sws1/sws1 flies (glial hyper-wrapping no longer occurs).

Expression of swsR133A.Scer\UAS driven pan-neuronally by Scer\GAL4Appl.G1a significantly (partially) rescues neuropil vacuolization in sws1/sws1 flies, though this rescue is significantly less than is seen with expression of swsScer\UAS.cMa (almost full rescue). Expression of swsS985D.Scer\UAS driven pan-neuronally by Scer\GAL4Appl.G1a partially rescues neuropil vacuolization in sws1/sws1 flies (though this rescue is less than is seen with expression of swsScer\UAS.cMa).

Neuronal expression of swsScer\UAS.cMa, under the control of Scer\GAL4elav-C155 rescues some aspects of sws1 neuronal degeneration, namely the vacuolisation in the neuropil.

Glial expression of swsScer\UAS.cMa, under the control of Scer\GAL4loco.1.3 rescues the glial phenotype found in sws1 mutants.

Expression of swsScer\UAS.cMa in either neurons or glia (under the control of either Scer\GAL4elav-C155 or Scer\GAL4loco.1.3) restores the wild-type NTE-like activity (NTE-neuropathy target esterase).

Images (0)
Mutant
Wild-type
Stocks (0)
Notes on Origin
Discoverer

Heisenberg.

Selected as: Anatomical defect (see FBrf0033934).

External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (2)
References (12)