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General Information
Symbol
Dmel\park1
Species
D. melanogaster
Name
FlyBase ID
FBal0189571
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Also Known As
parkin1
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
Cytology
Nature of the lesion
Statement
Reference

An insertion in position +988 of the park ORF, in the middle of exon 5.

Insertion components
P{EP}park1
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 )
Disease
Interaction
References
is ameliorated by GstO1UAS.cKa
is ameliorated by AMPKαTD.UAS
is ameliorated by Ucp4AUAS.cWa
is ameliorated by srlUAS.cTa
Comments on Models/Modifiers Based on Experimental Evidence ( 2 )
 

FlyBase curator comment: "Parkinson's disease 2" is associated with human PARKIN (the ortholog of park).

FlyBase curator comment: 'Parkinson's disease' subtype 'Parkinson's disease 2' is associated with gene PRKN.

Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In

mitochondrion & skeletal muscle of thorax

myofibril & skeletal muscle of thorax

Detailed Description
Statement
Reference

park1 adults show decreased climbing ability, indented adult thoraxes, wing posture defects; their flight muscles show increased apoptosis and swollen mitochondria; there is a decrease in the number of DA PMM1/2 and PPL1 neurons in the brain.

parkΔ21/park1 mutants exhibit muscle cell abnormalities and degeneration (accumulation of ubiquitin modified proteins and disordering of actin filaments) with large and dysmorphic mitochondria (Mito-GFP) when compared to controls. Also these mutants are incapable of flight.

park1/park1 adult flies have an increased duration of total activity and a shorter duration of nighttime sleep, but similar daytime sleep compared to controls. Under constant dark conditions, flies display a longer period of locomotor activity rhythm.

park1/parkΔ21 transheterozygous adults display aberrant wing posture, thoracic indentations and climbing ability deficit along with mitochondrial defects (loss of cristae) in indirect flight muscles.

park1/parkΔ21 transheterozygotes present mitochondria fragmentation, despite of normal cristae morphology, in adult indirect flight muscles, as compared to controls.

park1/park1 flies exhibit a significant decrease in climbing ability, and show mitochondrial defects in flight muscle, as compared to controls.

park1 homozygous mutant third instar larvae display deficit in locomotion: the crawling speed, distance from start to finish as well as the total length travelled over time are all significantly reduced in the mutant larvae compared to controls.

park1/park1 mutant larval muscles contain abnormal large and swollen mitochondria with disrupted cristae organization, adult indirect flight muscles in young (4-day-old) flies undergo apoptosis (assessed by TUNEL assay).

Mitochondria are mislocalized and clustered in park1/park1 or park1/Df(3L)Pc-MK germ cells in the ovary, and females have greatly reduced fertility (decreased egg-laying).

3-5 day old park1/park25 mutant flies show indirect flight muscle degeneration. One or several of the six muscles has highly degenerated, highly irregular myofibrils with abnormal sarcomere structure in 65% of the animals as compared to controls.

The indirect flight muscles of park1/park25 mutants display a heterogeneous population of mitochondria with the majority having significantly enlarged sizes and mild or severe disruption of their cristae structure, when compared to control mitochondria. Severely enlarged mitochondria are also seen in dopaminergic neurons.

park1/park25 mutants show reduced ATP content in the thorax to approximately 40% of controls. Complex 1 activity is not significantly different from controls.

park1/park1 mutants do not display any difference in the number of PPL1 neurons, as compared to controls.

The mitochondria in the flight muscles of park1 mutant flies are large compared to controls.

The indirect flight muscles of flies expressing parkSA.Scer\UAS under the control of Scer\GAL4da.PU in a parkΔ21/park1 mutant background contain abnormally fused mitochondria.

park1/park1 flies have a crushed thorax (significantly increased percentage of thoracic indentations), locomotor defects (significantly slower climbing), male sterility, degeneration (cell death) and disorganization and fewer mitochondrial cristae in indirect flight muscle.

The flight muscles of park1/parkΔ21 adults have swollen mitochondria.

The brains of park1 mutant third instar larvae are similar in size to wild type.

park1/parkΔ21 flies often have an abnormal wing posture, and mitochondrial aggregation is seen in the muscles.

park1 mutants show collapsed thorax and downturned wing phenotypes, due to degeneration of the IFMs.

park1 mutants show an age-dependent degeneration of DA neurons, especially in the protocerebral posterior lateral 1 (PPL1) cluster.

park1/park1 flies have a collapsed thorax phenotype, downturned wings, swollen mitochondria and signs of cell death in the indirect flight muscle (and levels of mtDNA and ATP are reduced), and show significant locomotor defects (reduced climbing ability) compared to controls.

park1 mutant flies exhibit climbing defects, loss of mitochondrial integrity in the indirect flight muscles and loss of dopaminergic neurons in the protocerebral posterior lateral 1 (PPL1) cluster. These phenotypes can all be significantly rescued upon treatment with EGCG. The climbing defects are also rescued with AICAR, a direct pharmacological activator of AMPK. Both the dopaminergic neuron and climbing defects are rescued upon treatment with another selective AMPK activator, metformin. Conversely, flies treated with a commonly used AMPK inhibitor, Compound C, exhibit markedly increased mortality.

The flight defects of park1/parkΔ21 animals are significantly improved by feeding with vitamin K[[2]] (MK-4 form tested).

The mitochondrial morphology defects of park1/parkΔ21 larvae are partially rescued by feeding with vitamin K[[2]] (MK-4 form tested).

The locomotive defect and reduced life span phenotypes of park1 mutants are not mitigated by feeding the mutant flies with linoleic acid and linolenic acid.

The mitochondrial derivatives in elongated spermatids of homozygous males are irregular and swollen. Only one mitochondrial derivative forms in hemizygous males during spermatogenesis.

Hemizygous females are sterile. Stage 5 follicles show severe mitochondrial clustering in nurse cells, and the clustering worsens with age. Clustering of mitochondria is also seen in the somatic follicle cells.

park1 fly brains show an obvious loss of dopaminergic neurons in the PPL1 cluster. This loss worsens with age. park1 fly brains also show loss of dopaminergic neurons in the PAM cluster, though other dopaminergic neuronal clusters, including PAL, PPL2, PPM1/2 and PPM3, are unaffected.

park1 flies show a significant impairment in the ability in their climbing ability at 10 days after eclosion which progressively worsens with age.

park1 flies are especially susceptible to rotenone-induced toxicity.

The indirect flight muscles of park1 flies show prominent mitochondrial defects.

Mutant adults often show a collapsed-thorax phenotype immediately after eclosion and they have a defective wing phenotype. Muscle fibres in the adult thorax are disorganised with enlarged mitochondria and apoptotic muscle cells are seen (in contrast to controls). Males are completely sterile due to defective Nebenkern.

park1 mutants exhibit reduced longevity, a drooped wing phenotype, locomotor dysfunction, and muscle degeneration, accompanied by apoptosis. park1 mutants exhibit a severe loss of dorsomedial dopaminergic neurons, with the remaining dorsomedial dopaminergic neurons exhibiting a shrunken morphology compared to the age-matched control. Feeding L-DOPA to park1 mutant flies significantly restores the climbing ability (up to approximately 70% of the unfed wild-type control), whereas D-DOPA has no effect.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
NOT Enhanced by
Suppressed by
Statement
Reference

park1 has visible | adult stage phenotype, suppressible | partially by UchKO/UchKO

park1 has visible phenotype, suppressible | partially by opa1-like[+]/Opa1EY09863

park1 has flightless phenotype, suppressible | partially by Df(1)dx81/+

NOT suppressed by
Statement
Reference

park1 has decreased cell number | adult stage phenotype, non-suppressible by UchV96M

park1 has increased cell death | adult stage phenotype, non-suppressible by UchH19Y

park1 has decreased cell number | adult stage phenotype, non-suppressible by UchH19Y

parkΔ21/park1 has abnormal flight phenotype, non-suppressible by mAcon11/Acon[+]

parkΔ21/park1 has abnormal flight phenotype, non-suppressible by mAcon1MB09176/Acon[+]

parkΔ21/park1 has male sterile phenotype, non-suppressible by Scer\NDI1UAS.cVa

park1 has flightless phenotype, non-suppressible by opa1-like[+]/Opa1EY09863

park1 has flightless phenotype, non-suppressible by Drp12/Drp1[+]

park1 has visible phenotype, non-suppressible by Drp12/Drp1[+]

park1 has visible phenotype, non-suppressible by Pink1UAS.Tag:HA/Scer\GAL4hs.PB

Enhancer of
Statement
Reference
NOT Enhancer of
Statement
Reference
Suppressor of
Other
Phenotype Manifest In
Enhanced by
NOT Enhanced by
Statement
Reference

parkΔ21/park1 has wing phenotype, non-enhanceable by Scer\GAL4da.PU/trcS292E.UAS.L

parkΔ21/park1 has wing phenotype, non-enhanceable by rictorUAS.cHa/Scer\GAL4da.PU

Suppressed by
Statement
Reference

park1 has mitochondrion | adult stage phenotype, suppressible by UchKO/UchKO

park1 has flight muscle | adult stage phenotype, suppressible by UchKO/UchKO

park1 has mitochondrion | adult stage phenotype, suppressible | partially by UchV96M

park1 has flight muscle | adult stage phenotype, suppressible | partially by UchV96M

park1 has flight muscle | adult stage phenotype, suppressible | partially by UchE8A

park1 has mitochondrion | adult stage phenotype, suppressible | partially by UchE8A

park1 has flight muscle | adult stage phenotype, suppressible by UchC93S

park1 has mitochondrion | adult stage phenotype, suppressible by UchC93S

park1 has adult thorax phenotype, suppressible by UchKO/UchKO

park1 has wing phenotype, suppressible | partially by UchKO/UchKO

park1 has wing phenotype, suppressible by Scer\GAL4how-24B/AMPKαTD.UAS

park1 has wing phenotype, suppressible by Df(1)dx81/+

park1 has adult thorax phenotype, suppressible by Df(1)dx81/+

park1 has wing phenotype, suppressible | partially by opa1-like[+]/Opa1EY09863

park1 has adult thorax phenotype, suppressible | partially by opa1-like[+]/Opa1EY09863

NOT suppressed by
Statement
Reference

park1 has mitochondrion | adult stage phenotype, non-suppressible by UchH19Y

park1 has flight muscle | adult stage phenotype, non-suppressible by UchH19Y

parkΔ21/park1 has wing phenotype, non-suppressible by rictorUAS.cHa/Scer\GAL4da.PU

parkΔ21/park1 has wing phenotype, non-suppressible by Scer\GAL4da.PU/trcS292E.UAS.L

park1 has adult thorax phenotype, non-suppressible by Sirt1UAS.cGa/Scer\GAL4arm.PU

park1 has wing blade phenotype, non-suppressible by Sirt1UAS.cGa/Scer\GAL4arm.PU

park1 has wing phenotype, non-suppressible by Drp12/Drp1[+]

park1 has adult thorax phenotype, non-suppressible by Drp12/Drp1[+]

park1 has wing phenotype, non-suppressible by Pink1UAS.Tag:HA/Scer\GAL4hs.PB

park1 has myofibril & skeletal muscle of thorax phenotype, non-suppressible by Pink1UAS.Tag:HA/Scer\GAL4hs.PB

park1 has mitochondrion & skeletal muscle of thorax phenotype, non-suppressible by Pink1UAS.Tag:HA/Scer\GAL4hs.PB

Enhancer of
Statement
Reference
Suppressor of
Other
Statement
Reference
Additional Comments
Genetic Interactions
Statement
Reference

The aberrant wing posture, thoracic indentations along with mitochondrial defects (loss of cristae) in indirect flight muscles observed in park1/parkΔ21 transheterozygous adults are all significantly rescued by Scer\GAL4Mhc.PU-driven expression of STUB1Scer\UAS.cCa, whereas their climbing ability deficit is not improved.

The reduced climbing ability of park1/parkΔ21 mutants is not exacerbated by combination with either STUB1I or STUB1II in homozygous state, but the lifespan of the double mutants is significantly decreased compared to park1/parkΔ21 single mutants.

The mitochondria morphology defects observed in the adult indirect flight muscles of park1/parkΔ21 transheterozygotes are not enhanced by Chchd2H43 homozygosity.

Expression of srlScer\UAS.cTa under the control of Scer\GAL4how-24B suppresses the climbing defects and mitochondrial defects seen in park1/park1 mutants.

park1/park1 suppresses the ability of Scer\GAL4GMR.PF>Atg1Scer\UAS.cSa to suppress age-dependent retinal degeneration (loss of rhabdomeres from photoreceptors) in trpP365/+ flies.

Neither the swollen mitochondria phenotype nor the the locomotion deficit characteristic for park1 homozygous mutant third instar larvae can be suppressed by Scer\GAL4Mef2.PR-driven expression of cluUAS.Tag:MYC.

cluΔW/+;park1/+ double heterozygous larvae show abnormal clustering of mitochondria around nuclei in muscle cells that is not observed in either of the single heterozygotes.

The mitochondrial morphology defects observed in larval muscles of both cluΔW and park1 homozygotes are exacerbated further in the double mutants, moreover while either cluΔW or park1 are partially lethal with about 5-10% of adult escapers, cluΔW/cluΔW;park1/park1 mutants do not yield any viable adults. On the other hand the larval locomotor deficit of either of the single mutants is not significantly worsened in the double mutants.

Expression of RetMEN2B.Scer\UAS under the control of Scer\GAL4Mef2.PR does not suppress the muscle morphology phenotype seen in the indirect flight muscles of park1/park25 mutants. The frequency of flies with "actin blobs" is decreased markedly compared to RetMEN2B.Scer\UAS expressing controls. The structural impairments seen in park1/park25 mutant mitochondria are not suppressed. The reduction in thoracic ATP levels is not rescued.

Expression of RetMEN2B.Scer\UAS under the control of Scer\GAL4Mhc.PK (limited to the pharate adult stages onwards using Scer\GAL80ts.αTub84B) does not suppress the muscle morphology phenotype seen in the indirect flight muscles of park1/park25 mutants.

Expression of RetMEN2B.Scer\UAS under the control of Scer\GAL4ple.PF does not suppress the mitochondrial morphology defects seen in park1/park25 mutant dopaminergic neurons.

Overexpression of Ucp4AScer\UAS.cWa by Scer\GAL4Act.PU reduces thoracic indentations, locomotor defects, male sterility, degeneration (cell death) and disorganization and fewer mitochondrial cristae in indirect flight muscle in park1/park1 flies.

The mitochondria morphological defects seen in park1/parkΔ21 adults are not rescued by Acon1/+ or AconMB09176/+.

park1 suppresses the enlarged brain phenotype seen in l(2)gl1/l(2)gl4 mutant third instar larvae.

The brains of clu169 park1 double mutant flies are similar in size to wild type.

Expression of either rictorScer\UAS.cHa or trcS292E.Scer\UAS under the control of Scer\GAL4da.PU fails to rescue the abnormal wing posture and mitochondrial aggregation phenotypes seen in park1/parkΔ21 flies.

GstO21/park1 double mutants show dramatically enhanced degeneration of the indirect flight muscles compared with park1 single mutants.

20-day-old park1/GstO21 double mutants show significantly increased DA neuron degeneration in the PPL1 cluster compared to park1 single mutants of the same age, whereas there is no difference in neuronal degeneration between park1/GstO21 double mutants and park1 single mutants in 1-day-old flies.

Expression of GstO2A.Scer\UAS using the muscle-specific driver Scer\GAL4how-24B significantly suppresses both the thorax and downturned wing phenotypes found in park1 mutants.

Expression of GstO2B.Scer\UAS using the muscle-specific driver Scer\GAL4how-24B does not affect either of the thorax and downturned wing phenotypes found in park1 mutants.

Expression of GstO1Scer\UAS.cKa using the muscle-specific driver Scer\GAL4how-24B does not affect either of the thorax and downturned wing phenotypes found in park1 mutants.

Expression of GstO2C31A.A.Scer\UAS using the muscle-specific driver Scer\GAL4how-24B does not affect either of the thorax and downturned wing phenotypes found in park1 mutants.

Overexpression of GstO2A.Scer\UAS under the control of Scer\GAL4αTub84B.PL, a ubiquitous driver, suppresses the degeneration of IFMs in park1 mutants. Overexpression results in regular and compact muscle tissues in the dorsal longitudinal IFMs, which are similar to those of wild-type flies except for occasional vacuoles. Overexpression of GstO2A.Scer\UAS appears to prevent degeneration of the IFMs by blocking the activation of the JNK pathway and apoptosis in park1 mutants.

Overexpression of GstO2A.Scer\UAS under the control of Scer\GAL4ple.PF results in significant restoration of the lost DA neurons in 20-day-old park1 mutant flies.

Expression of ATPsyn-βNIG.11154R at 18[o]C in the muscle, under the control of Scer\GAL4how-24B enhances the downturned wing and collapsed thorax phenotype found in park1 mutants, compared to park1 single mutants.

Expression of Sirt1Scer\UAS.cGa driven by Scer\GAL4arm.PU does not suppress phenotypes (collapsed thorax, downturned wings, swollen mitochondria along with increased cell death and reduced levels of mtDNA and ATP in the indirect flight muscle and locomotor defects) seen in Pink1B9/Y flies.

Expression of SNF1ATD.Scer\UAS under the control of Scer\GAL4how-24B suppresses the mitochondrial abnormalities and climbing ability defects seen in park1 mutant flies. The wing posture defects seen in park1 mutant flies are also rescued.

Mitochondria are noticeably clustered in the follicles of park1/+ ; cluEP969/+ females, although both male and female park1/+ ; cluEP969/+ animals are fertile.

Expression of parkScer\UAS.T:Zzzz\FLAG,T:Hsap\COX4I1 under the control of Scer\GAL4hs.PB suppresses the mitochondrial swelling phenotype in Pink1B9, park1 double mutants to a great extent.

Expression of parkScer\UAS.T:Hsap\MYC under the control of Scer\GAL4hs.PB partially suppresses the mitochondrial swelling phenotype in Pink1B9, park1 double mutants.

Expression of parkT187A.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4hs.PB partially suppresses the mitochondrial swelling phenotype in Pink1B9, park1 double mutants.

The defective wing and thorax phenotypes seen in park1 mutant flies are not rescued by expression of Pink1Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4hs.PB. Expression of Pink1Scer\UAS.T:Ivir\HA1 under the control of Scer\GAL4hs.PB also fails to rescue the enlarged mitochondria and apoptotic muscle cells seen in adult park1 thoracic muscles.

The thoracic muscle defects seen in park1 Pink1B9 double mutant flies are not increased in severity compared to either single mutant.

Xenogenetic Interactions
Statement
Reference

Overexpression of Pink1Scer\UAS.T:Ivir\HA1 in heterozygous park1 flies which also express Scer\GAL4elav.PU>Hsap\HTTQ93.ex1p.Scer\UAS fails to increase life span.

Overexpression of Pink1Scer\UAS.T:Ivir\HA1 in heterozygous park1 flies which also express Scer\GAL4elav.PU>Hsap\HTTQ93.ex1p.Scer\UAS fails to provide protection against photoreceptor degeneration.

Scer\NDI1Scer\UAS.cVa in the absence of a Scer\GAL4 driver does not suppress the sterility of park1/parkΔ21 males (even though Scer\NDI1Scer\UAS.cVa in the absence of a Scer\GAL4 driver does suppress the male sterility of Pink1B9 males).

Expression of Scer\NDI1Scer\UAS.cVa under the control of Scer\GAL4da.G32 does not suppress the flight defects or defects in mitochondrial morphology which are seen in park1/parkΔ21 flies.

Scer\GAL4Ddc.PL-mediated expression of Hsap\PARK2R275W.Scer\UAS does not affect the reduction in dopaminergic neurons in the PPL1 and PAM clusters seen in 20-day old park1 flies.

Scer\GAL4Ddc.PL-mediated expression of Hsap\PARK2WT.Scer\UAS significantly protects against the degeneration of PPL1 and PAM dopaminergic neurons normally seen in 20-day old park1 flies.

park1 flies that also carry Scer\GAL4Ddc.PL, Hsap\PARK2R275W.Scer\UAS are poorer climbers than either single genotype alone.

The mitochondrial defects seen in park1 indirect flight muscles are significantly mitigated by Scer\GAL4how-24B-mediated expression of Hsap\PARK2WT.Scer\UAS.

The mitochondrial defects seen in park1 indirect flight muscles persist when Hsap\PARK2R275W.Scer\UAS is expressed using Scer\GAL4how-24B.

Complementation and Rescue Data
Partially rescued by
Comments

Expression of parkScer\UAS.cSa under the control of Scer\GAL4da.PU rescues the mitochondria phenotype seen in parkΔ21/park1 mutant indirect flight muscles. The reduction in ATP levels is also rescued, and is improved to a level higher than that of controls.

Expression of parkScer\UAS.cSa under the control of Scer\GAL4Mhc.PU rescues the wing posture and thorax defects seen in parkΔ21/park1 mutant flies.

Expression of parkSA.Scer\UAS under the control of Scer\GAL4da.PU fails to rescue the mitochondria phenotype seen in parkΔ21/park1 mutant indirect flight muscles. The reduction in ATP levels is rescued, and is improved to a level higher than that of controls.

Expression of parkSA.Scer\UAS under the control of Scer\GAL4Mhc.PU partially rescues the wing posture and thorax defects seen in parkΔ21/park1 mutant flies. The reduction in ATP levels is also improved.

Expression of parkSE.Scer\UAS under the control of Scer\GAL4da.PU results in lethality, either in a parkΔ21/park1 or wild type mutant background.

The mitochondrial morphology in the indirect flight muscle of park1 mutants is fully rescued by expression of parkScer\UAS.T:Hsap\MYC under the control of Scer\GAL4hs.PB

The mitochondrial morphology in the indirect flight muscle of park1 mutants is partially rescued by expression of parkT187A.Scer\UAS.T:Hsap\MYC under the control of Scer\GAL4hs.PB

The park1 dorsomedial dopaminergic neuron morphology and loss phenotype can be completely rescued by the expression of parkScer\UAS.T:Hsap\MYC under the control of Scer\GAL4Ddc.PL.

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Mutant
Wild-type
Stocks (1)
Notes on Origin
Discoverer
External Crossreferences and Linkouts ( 0 )
Synonyms and Secondary IDs (9)
References (43)