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General Information
Symbol
Hsap\SNCAA30P.UAS
Species
H. sapiens
Name
FlyBase ID
FBal0104768
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
UAS-A30P, UAS-A30P α-synuclein, P{UAS-syn.A30P}, UAS-SNCAA30P
Key Links
Allele class
Nature of the Allele
Allele class
Mutations Mapped to the Genome
 
Type
Location
Additional Notes
References
Associated Sequence Data
DNA sequence
Protein sequence
 
 
Progenitor genotype
Carried in construct
Cytology
Nature of the lesion
Statement
Reference

UASt regulatory sequences drive expression of the mutated A30P form of Hsap\SNCA (which is linked to a familial Parkinson's disease in humans).

Allele components
Product class / Tool use(s)
Encoded product / tool
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 )
Comments on Models/Modifiers Based on Experimental Evidence ( 1 )
 

FlyBase curator comment: "Parkinson's disease 1" is associated with mutations in human SNCA.

Disease-implicated variant(s)
 
This allele represents a human variant implicated in disease.
SNCA:p.Ala30Pro
Variants Synonym(s)
Associated human disease model(s)
External database links
Comments concerning this variant
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

The expression of Hsap\SNCAA30P.UAS under the control of Scer\GAL4GMR.long leads to progressive retinal generation: while 1-day old adults show normal retinal morphology, 30-days old adults show severe defects, namely apparent loss of photoreceptor neurons along with vacuole formation.

Adults expressing Hsap\SNCAA30P.UAS under the control of Scer\GAL4Ddc.PU show age-dependent impairment in climbing ability, associated with a progressive decrease in PPM3 neurons, despite of no significant changes in other DA neurons (PAL, PPM1/2, PPL1 and PPL2 clusters) as compared to controls.

The expression of Hsap\SNCAA30P.UAS under the control of Scer\GAL4elav.PU leads to a progressive decline in adult locomotion capacity (i.e. climbing assays), as compared to controls.

Expressing Hsap\SNCAA30P.UAS under the control of Scer\GAL4ple.PF induces a progressive decrease in adult climbing capacity and results in 21-days old adults raised at 29[o]C exhibiting significantly fewer PPL1 neurons than age-matched controls; there is no obvious effect on lifespan.

Individuals expressing Hsap\SNCAA30P.UAS under the control of Scer\GAL4elav-C155 present a progressive decrease in climbing ability, as compared to controls

Adult flies expressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4ple.PF fed with 1% glucose show a significantly lower survival rate and loss of dopaminergic neurons in the PPM1/2 cluster (other dopaminergic neuronal clusters - VUM, PAL, PPM3, PPL1 and PPL2 - are unaffected) but their locomotion (climbing ability) at 0-5 days post-eclosion is not impaired relative to wild-type.

Expression of Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4elav-C155 results in a significant reduction in lifespan as compared to controls. These flies exhibit a significantly lower sedation time in response to acute ethanol exposure, and also show a significant longer recovery time, as compared to controls.

Flies expressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4elav-C155 show defects in climbing ability. This phenotype is partially suppressed when the flies are fed the natural antioxidant decalepis hamiltonii (Dh).

Locomotor rhythm and level of physical activity are disrupted in flies expressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4elav-C155. This is partially suppressed when the flies are fed the natural antioxidant decalepis hamiltonii (Dh).

Expression of Hsap\SNCAA30P.Scer\UAS under the control Scer\GAL4elav-C155 leads to a decrease in lifespan, loss of dopaminergic cells, and progressive climbing defects, as compared to controls

Expression of Hsap\SNCAA30P.Scer\UAS driven by Scer\GAL4nSyb.PU leads to significant defects in climbing ability in 15 day old flies; climbing performance in mutants is significantly improved by administration of L-DOPA. 30 day old Scer\GAL4nSyb.PU>Hsap\SNCAA30P.Scer\UAS flies have significantly fewer dopamine neurons in the dorsomedial cluster, compared to controls.

Male Scer\GAL4nSyb.PU>Hsap\SNCAA30P.Scer\UAS flies that have been starved for 8 hours (to elevate baseline walking activity) show significant age-dependent (15 vs 30 day old) walking deficits (total distance walked, distance per episode, walking duration per episode, velocity, angular velocity and walking frequency) in an open field assay (no significant differences in controls). Young mutants do not show significant deficits compared to young controls, while aged mutants show significant defects in total distance walked, distance per episode, velocity and angular velocity compared to aged controls. Scer\GAL4nSyb.PU>Hsap\SNCAA30P.Scer\UAS aged males are significantly more centrophobic than young mutants, possibly showing elevated anxiety.

Ectopic expression of Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4elav.PU results in an age-progressive deficit in climbing behavior as well as age-progressive impairment in odor acuity and odor discrimination (the olfaction defects are displayed even before the motor deficit is first manifested) in adult flies compared to wild-type controls. The odor discrimination deficit is not odor-specific.

The defective olfaction (odor acuity and odor discrimination impairment) seen in adult flies expressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4elav.PU is (unlike in wild-type controls) further worsened under oxidative stress condition.

Impaired olfaction (deficit in both odor acuity and odor discrimination) is seen in adult flies expressing Hsap\SNCAA30P.Scer\UAS under the control of the Scer\GAL4ple.PU driver but not when expressed using the Scer\GAL4ChAT.PU or the Scer\GAL4Orco.PU driver.

Expression of Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4ple.PF does not result in a loss of dopaminergic neurons in 55-day old flies.

Flies expressing Hsap\SNCAA30P.Scer\UAS under the control of either Scer\GAL4elav-C155, Scer\GAL4Ddc.PL or Scer\GAL4NP6510 show an accelerated age-dependent decline in locomotor performance in a startle-induced negative geotaxis (SING) assay compared to controls.

Expression of Hsap\SNCAA30P.Scer\UAS under the control of either Scer\GAL4ple.PF or Scer\GAL4Trh.PB has no significant effect on locomotor performance in a SING assay.

Flies expressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4GMR58E02 show an accelerated age-dependent decline in locomotor performance in a SING assay compared to Scer\GAL4GMR58E02 controls (which themselves show faster decline in the SING assay than wild type).

Expression of Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4NP6510 results in an apparent decrease in Scer\GAL4NP6510-positive dopaminergic terminals connected to the middle part of the mushroom body β lobes and the tip of the β' lobes in 3 day old flies compared to wild-type controls (analysed using the "split-GFP reconstitution across synaptic partners" (GRASP) technique). In 20 day old mutant flies there is an almost complete disappearance of dopaminergic connections, particularly in the β' lobes. There is no overt loss of dopaminergic neuron cell bodies in the protocerebral anterior medial cluster and projections of non-dopaminergic Scer\GAL4NP6510-positive neurons towards the fan-shaped bodies are normal.

Flies expressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4elav-C155 exhibit a 59% licking activity and 50.7% attempted copulation activity, relative to wild-type. These flies exhibit 27.3% fewer copulations compared to wild-type. Hsap\SNCAA30P.Scer\UAS-expressing males perform less sexual activity, relative to Oregon-R males.

Expression of Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4elav-C155 does not affect climbing ability at 6 days of age. Measurement at 21 days reveals significant locomotor dysfunction, reflecting a 28% reduction in climbing ability.

Three-day-old flies overexpressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4ple.PF show a 20% reduction in the number of dopaminergic neurons compared to control flies. In 35-day-old flies there is an additional decrease in the number of dopaminergic neurons by 28% compared to those observed in 3-day-old flies, while control flies show no significant neurodegeneration.

Overexpression of Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4ple.PF leads to an age-dependent decline in motor abilities. However, climbing ability is not affected.

Flies expressing Hsap\SNCAA30P.Scer\UAS in dopaminergic neurons under the control of Scer\GAL4ple.PF exhibit age-dependent neurodegeneration. No neuron loss is seen at days 15, but increased neurodegeneration compared to controls is seen by 25 days. No loss of dopaminergic neurons is seen in age-matched wild type flies.

Expression of Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4ple.PF enhances the hypoxia-induced dopaminergic neuron degeneration seen in control flies.

20 day old flies expressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4elav.PU show a loss of dorsomedial dopamine neurons in the brain.

20 day old flies expressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4Ddc.PL have a 50% reduction in the number of dopaminergic neurons in the dorsomedial clusters of the brain.

20 day old flies expressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4Ddc.PL show marked loss of neurons in the dorsomedial dopaminergic clusters. Neuron loss is more variable in the dorsolateral-1 dopaminergic clusters, ranging from no loss of neurons to as much as 50% of neurons being lost.

Expression of Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4Cha.7.4 does not affect cholinergic neurons in the optic lamina.

Overall brain volume, including the outer cellular cortex layer containing neuronal and glial cell bodies and central neuropil areas, and overall brain architecture are preserved in 60 day old flies expressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4elav.PLu. These flies show a marked, age-dependent loss of dorsomedial dopaminergic neurons. All the major serotonergic cell groups are present in 30 day old flies. Hsap\SNCA inclusions in the brain (detected by immunostaining) are seen in aged flies (the inclusions are first seen at 20-30 days of age). Most neuronal cytoplasmic inclusions are single, round and regular, although a few are more irregular. The inclusions have a relatively homogeneous core and are edged by radiating filaments projecting into a surrounding halo. The filaments are 7-10nm in diameter and are sometimes associated with cellular organelles. Granular material is intermixed with loosely packed filaments in less compact inclusions. Neuritic Hsap\SNCA inclusions are also present in the brain and consist of both thread- and grain-like inclusions. Locomotor behaviour is grossly preserved in young flies expressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4elav.PLu. These flies initially climb as well as wild-type flies, but over time they show a premature loss of climbing ability compared to control flies. Flies expressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4GMR.PF show retinal degeneration that is detectable by 10 days, and marked at 30 days after eclosion.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressed by
Statement
Reference
Phenotype Manifest In
Suppressed by
Statement
Reference
Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
Statement
Reference

The number of dopaminergic neurons in Hsap\SNCAA30P.Scer\UAS flies also expressing pleGD1181 does not change from 3 to 35 days indicating a strong suppression effect by the pleGD1181 line (when both are expressed under the control of Scer\GAL4ple.PF).

Co-expression of pleGD1181 with Hsap\SNCAA30P.Scer\UAS (both under the control of Scer\GAL4ple.PF) rescues the age-dependent decline in motor abilities seen upon Hsap\SNCAA30P.Scer\UAS overexpression.

Expression of Hsap\SOD1Scer\UAS.cPa suppresses the dopaminergic neuron degeneration seen when Hsap\SNCAA30P.Scer\UAS is expressed under the control of Scer\GAL4ple.PF. The reduction in climbing ability is also suppressed.

Sin3A08269 rescues the progressive loss of dorsomedial dopamine neurons in the brain seen in flies expressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4elav.PU.

The reduction in the number of dopaminergic neurons in the dorsomedial clusters of the brain seen in 20 day old flies expressing Hsap\SNCAA30P.Scer\UAS under the control of Scer\GAL4Ddc.PL is suppressed by coexpression of Hsap\PARK2Scer\UAS.cYa.

Complementation and Rescue Data
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Mutant
Wild-type
Stocks (1)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (2)
Reported As
Symbol Synonym
Hsap\SNCAA30P.Scer\UAS
Hsap\SNCAA30P.UAS
Name Synonyms
Secondary FlyBase IDs
    References (33)