FlyBase Allele Report: Hsap\LRRK2[I2020T.UAS]

General Information

Symbol

Hsap\LRRK2^I2020T.UAS

Species

H. sapiens

Name

FlyBase ID

FBal0244982

Feature type

allele

Associated gene

Hsap\LRRK2

Associated Insertion(s)

Carried in Construct

P{UAS-hLRRK2.I2020T}

Also Known As

UAS-hLRRK2 I2020T

Key Links

Transgenic product class

missense_variant

(Venderova et al., 2009)

Mutagen

in vitro construct

Nature of the Allele

Transgenic product class

missense_variant

(Venderova et al., 2009)

Mutagen

in vitro construct

(Venderova et al., 2009)

Progenitor genotype

Carried in construct

P{UAS-hLRRK2.I2020T}

Cytology

Description

UASt regulatory sequences drive expression of a mutant form of Hsap\LRRK2, which contains the amino acid replacement I2020T.

(Venderova et al., 2009)

Allele components

Component

Use(s)

Regulatory region(s)

UASt

binary expression system - regulatory region

Encoded product / tool

Hsap\LRRK2

Mutations Mapped to the Genome

Curation Data

Type

Location

Additional Notes

References

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 Parkinson's disease 8

CEA

(Linhart et al., 2014)

model of Parkinson's disease

CEA

(Cording et al., 2017, Penney et al., 2016, Venderova et al., 2009)

Modifiers Based on Experimental Evidence ( 1 )

Disease

Interaction

References

model of Parkinson's disease 8

is ameliorated by Vps35^EY14200

(Linhart et al., 2014)

is ameliorated by Vps26^G2008

(Linhart et al., 2014)

model of Parkinson's disease

is ameliorated by Hsap\PRKN^UAS.cYa

(Venderova et al., 2009)

is ameliorated by Hsap\PINK1^UAS.cYa

(Venderova et al., 2009)

is ameliorated by Hsap\PARK7^UAS.cYa

(Venderova et al., 2009)

is exacerbated by Hsap\PINK1^UAS.cYa

(Venderova et al., 2009)

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

Disease-implicated variant(s)

This allele represents a human variant implicated in disease.

(Venderova et al., 2009)

LRRK2:p.Ile2020Thr

(FlyBase curators, 2019-)

Variants Synonym(s)

Associated human disease model(s)

Parkinson disease 8

External database links

ClinVar: LRRK2_1941

Comments concerning this variant

Phenotypic Data

Phenotypic Class

abnormal feeding behavior | adult stage, with Scer\GAL4^ple.PF

(Cording et al., 2017)

abnormal feeding behavior | adult stage, with Scer\GAL4^ple.TH-C'

(Cording et al., 2017)

abnormal feeding behavior | adult stage, with Scer\GAL4^ple.TH-D'

(Cording et al., 2017)

abnormal locomotor behavior | adult stage, with Scer\GAL4^Ddc.PU

(Linhart et al., 2014)

abnormal neuroanatomy | adult stage, with Scer\GAL4^ple.PF

(Venderova et al., 2009)

abnormal neurophysiology | third instar larval stage, with Scer\GAL4^Mhc.PW

(Penney et al., 2016)

chemical sensitive, with Scer\GAL4^da.G32

(Venderova et al., 2009)

long lived, with Scer\GAL4^da.G32

(Venderova et al., 2009)

short lived, with Scer\GAL4^Ddc.PU

(Linhart et al., 2014)

short lived, with Scer\GAL4^ple.PF

(Cording et al., 2017)

visible, with Scer\GAL4^GMR.PF

(Venderova et al., 2009)

visible, with Scer\GAL4^GMR.PU

(Linhart et al., 2014)

Phenotype Manifest In

Detailed Description

Statement

Reference

The expression of Hsap\LRRK2^{I2020T.Scer\UAS} under the control of Scer\GAL4^ple.PF, Scer\GAL4^ple.TH-C' or Scer\GAL4^ple.TH-D', but not if under the control of Scer\GAL4^Ddc.PL or Scer\GAL4^Ddc.HL9, leads to a significant decrease in proboscis extension reflex (in starved flies exposed to a moderate sugar stimulus) in 3 to 18 days old adults, as compared to controls; these flies exhibit a significantly slower proboscis extension speed compared to controls. In ad libitum conditions, Scer\GAL4^ple.PF-driven expression leads to a significant decrease in lifespan compared to controls.

(Cording et al., 2017)

Expression of Hsap\LRRK2^{I2020T.Scer\UAS} under the control of Scer\GAL4^Mhc.PW does not result in any significant difference in amplitude of miniature excitatory junction currents (mEJCs), but does lead to an increase in amplitude of EJCs, and an increase in quantal content of larval neuromuscular junctions, as compared to controls.

(Penney et al., 2016)

Expression of Hsap\LRRK2^{I2020T.Scer\UAS} driven by Scer\GAL4^GMR.PU at 29[o]C causes a rough eye phenotype with pigmentation deficits (presence of black lesions, significantly increased compared to controls). Expression of Hsap\LRRK2^{I2020T.Scer\UAS} driven by Scer\GAL4^Ddc.PU causes significant locomotor deficits (reduced climbing ability) in 5 or 10 (but not 20, when all flies including controls show age-dependent locomotor deficits) day old flies, and significantly shortens lifespan, compared to controls.

(Linhart et al., 2014)

Flies expressing Hsap\LRRK2^{I2020T.Scer\UAS} under the control of Scer\GAL4^ple.PG do not show a progressive reduction in electroretinogram amplitude (there is no significant difference in the amplitude seen in 3 and 28 day old flies).

(Hindle et al., 2013)

Expression of Hsap\LRRK2^{I2020T.Scer\UAS} under the control of Scer\GAL4^GMR.PF does not result in any apparent eye degeneration.

(Kanao et al., 2010)

Expression of Hsap\LRRK2^{I2020T.Scer\UAS} under the control of Scer\GAL4^elav.PU has no effect on axonal growth in embryonic development.

10 day old and 50 day old adults expressing Hsap\LRRK2^{I2020T.Scer\UAS} under the control of Scer\GAL4^ple.PF at room temperature show loss of dopaminergic neurons in the dorsomedial posterior protocerebral clusters (PPM1/2) and in the dorsolateral posterior protocerebral cluster (PPL1) of the brain compared to control flies of the same age. A similar loss of neurons is seen in 20 day old adults expressing Hsap\LRRK2^{I2020T.Scer\UAS} under the control of Scer\GAL4^ple.PF at 29[o]C.

Expression of Hsap\LRRK2^{I2020T.Scer\UAS} under the control of Scer\GAL4^da.G32 at room temperature significantly extends the basal lifespan of flies compared to controls, while expression of Hsap\LRRK2^{I2020T.Scer\UAS} under the control of Scer\GAL4^elav.PU at room temperature or at 29[o]C has no significant effect on basal lifespan.

Flies expressing Hsap\LRRK2^{I2020T.Scer\UAS} under the control of Scer\GAL4^da.G32 have a significantly greater number of progeny compared with control flies.

Flies expressing Hsap\LRRK2^{I2020T.Scer\UAS} under the control of Scer\GAL4^da.G32 at room temperature show a greater sensitivity to chronic exposure to low levels of rotenone then control flies.

Flies expressing Hsap\LRRK2^{I2020T.Scer\UAS} under the control of Scer\GAL4^GMR.PF at 29[o]C show loss of pigmentation in the eyes. Significantly more black lesions are seen in the mutant eyes than in controls. Ultrastructurally, severe disruption of the regular trapezoidal arrangement of the photoreceptor cells is seen. The cell lattice between photoreceptor cell arrays of different ommatidia is completely absent and the ommatidia are sometimes fused together. Large holes are often seen in the eye sections.

(Venderova et al., 2009)

External Data

Linkouts

Interactions

Show genetic interaction network for Enhancers & Suppressors

Phenotypic Class

NOT Enhanced by

Statement

Reference

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PU has visible phenotype, non-enhanceable by Vps26^HMS01769, Scer\GAL4^GMR.PU

(Linhart et al., 2014)

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^Ddc.PU has abnormal locomotor behavior | adult stage phenotype, non-enhanceable by Vps35^HMS01858, Scer\GAL4^Ddc.PU

(Linhart et al., 2014)

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^Ddc.PU has abnormal locomotor behavior | adult stage phenotype, non-enhanceable by Vps29^HMS01877, Scer\GAL4^Ddc.PU

(Linhart et al., 2014)

Suppressed by

Statement

Reference

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PU has visible phenotype, suppressible by Vps35^EY14200, Scer\GAL4^GMR.PU

(Linhart et al., 2014)

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^Ddc.PU has abnormal locomotor behavior | adult stage phenotype, suppressible by Vps26^G2008, Scer\GAL4^Ddc.PU

(Linhart et al., 2014)

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^Ddc.PU has abnormal locomotor behavior | adult stage phenotype, suppressible by Vps35^EY14200, Scer\GAL4^Ddc.PU

(Linhart et al., 2014)

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^Ddc.PU has short lived phenotype, suppressible by Vps35^EY14200, Scer\GAL4^Ddc.PU

(Linhart et al., 2014)

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PU has visible phenotype, suppressible | partially by Vps26^G2008, Scer\GAL4^GMR.PU

(Linhart et al., 2014)

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PF has visible phenotype, suppressible | partially by Hsap\PINK1^UAS.cYa, Scer\GAL4^GMR.PF

(Venderova et al., 2009)

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PF has visible phenotype, suppressible | partially by Hsap\PRKN^UAS.cYa, Scer\GAL4^GMR.PF

(Venderova et al., 2009)

Enhancer of

Statement

Reference

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PF is an enhancer of visible phenotype of Scer\GAL4^GMR.PF, foxo^UAS.cKb

(Kanao et al., 2010)

NOT Enhancer of

Statement

Reference

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PU is a non-enhancer of visible phenotype of Scer\GAL4^GMR.PU, Vps26^HMS01769

(Linhart et al., 2014)

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^Ddc.PU is a non-enhancer of abnormal locomotor behavior | adult stage phenotype of Scer\GAL4^Ddc.PU, Vps35^HMS01858

(Linhart et al., 2014)

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^Ddc.PU is a non-enhancer of abnormal locomotor behavior | adult stage phenotype of Scer\GAL4^Ddc.PU, Vps29^HMS01877

(Linhart et al., 2014)

NOT Suppressor of

Statement

Reference

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PF is a non-suppressor of visible phenotype of Hsap\PRKN^UAS.cYa, Scer\GAL4^GMR.PF

(Venderova et al., 2009)

Phenotype Manifest In

NOT Enhanced by

Statement

Reference

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PU has eye | adult stage phenotype, non-enhanceable by Vps26^HMS01769, Scer\GAL4^GMR.PU

(Linhart et al., 2014)

Suppressed by

Statement

Reference

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PU has eye | adult stage phenotype, suppressible | partially by Vps26^G2008, Scer\GAL4^GMR.PU

(Linhart et al., 2014)

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PU has eye | adult stage phenotype, suppressible by Vps35^EY14200, Scer\GAL4^GMR.PU

(Linhart et al., 2014)

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PF has eye phenotype, suppressible | partially by Hsap\PINK1^UAS.cYa, Scer\GAL4^GMR.PF

(Venderova et al., 2009)

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PF has eye phenotype, suppressible | partially by Hsap\PRKN^UAS.cYa, Scer\GAL4^GMR.PF

(Venderova et al., 2009)

NOT suppressed by

Statement

Reference

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PF has pigment cell phenotype, non-suppressible by Hsap\PINK1^UAS.cYa, Scer\GAL4^GMR.PF

(Venderova et al., 2009)

Enhancer of

Statement

Reference

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PF is an enhancer of eye phenotype of Scer\GAL4^GMR.PF, foxo^UAS.cKb

(Kanao et al., 2010)

NOT Enhancer of

Statement

Reference

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PU is a non-enhancer of eye | adult stage phenotype of Scer\GAL4^GMR.PU, Vps26^HMS01769

(Linhart et al., 2014)

NOT Suppressor of

Statement

Reference

Hsap\LRRK2^I2020T.UAS, Scer\GAL4^GMR.PF is a non-suppressor of eye phenotype of Hsap\PRKN^UAS.cYa, Scer\GAL4^GMR.PF

(Venderova et al., 2009)

Additional Comments

Genetic Interactions

Statement

Reference

Xenogenetic Interactions

Statement

Reference

Co-expression of Vps26^G2008 or Vps35^EY14200 significantly suppresses eye phenotypes (presence of black lesions in around 50% of flies) in flies with expression of Hsap\LRRK2^{I2020T.Scer\UAS} driven by Scer\GAL4^GMR.PU at 29[o]C. Co-expression of Vps26^G2008 significantly suppresses locomotor deficits in flies with expression of Hsap\LRRK2^{I2020T.Scer\UAS} driven by Scer\GAL4^Ddc.PU. Co-expression of Vps35^EY14200 significantly suppresses locomotor deficits and shortened lifespan in flies with expression of Hsap\LRRK2^{I2020T.Scer\UAS} driven by Scer\GAL4^Ddc.PU.

Co-expression of Vps26^HMS01769 does not significantly enhance eye phenotypes (presence of black lesions) in flies with expression of Hsap\LRRK2^{I2020T.Scer\UAS} driven by Scer\GAL4^GMR.PU. Co-expression of Vps29^HMS01877 or Vps35^HMS01858 does not significantly enhance locomotor deficits in flies with expression of Hsap\LRRK2^{I2020T.Scer\UAS} driven by Scer\GAL4^Ddc.PU.

(Linhart et al., 2014)

The severity of the eye defects caused by expression of foxo^Scer\UAS.cKb under the control of Scer\GAL4^GMR.PF are enhanced by co-expression of Hsap\LRRK2^{I2020T.Scer\UAS}.

(Kanao et al., 2010)

Co-expression of Hsap\PINK1^Scer\UAS.cYa does not significantly suppress the loss of pigmentation in the eye, the roughness of the eye surface or the formation of holes in eye sections that are seen in flies expressing Hsap\LRRK2^{I2020T.Scer\UAS} under the control of Scer\GAL4^GMR.PF at 29[o]C, but the formation of black lesions in the eye is partially suppressed.

The formation of black lesions in the eye seen in flies expressing Hsap\LRRK2^{I2020T.Scer\UAS} under the control of Scer\GAL4^GMR.PF is suppressed by co-expression of Hsap\PARK2^Scer\UAS.cYa.

(Venderova et al., 2009)

Complementation and Rescue Data

Comments

Images (0)

Mutant

Wild-type

Stocks (0)

Notes on Origin

Discoverer

External Crossreferences and Linkouts ( 0 )

Synonyms and Secondary IDs (2)

Reported As

Symbol Synonym

Hsap\LRRK2^{I2020T.Scer\UAS}

Hsap\LRRK2^I2020T.UAS

Name Synonyms

Secondary FlyBase IDs

References (10)

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