FlyBase Allele Report: Hsap\LRRK2[I1122V.UAS]

General Information

Symbol

Hsap\LRRK2^I1122V.UAS

Species

H. sapiens

Name

FlyBase ID

FBal0244980

Feature type

allele

Associated gene

Hsap\LRRK2

Associated Insertion(s)

Carried in Construct

P{UAS-hLRRK2.I1122V}

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.I1122V}

Cytology

Description

UASt regulatory sequences drive expression of a mutant form of Hsap\LRRK2, which contains the amino acid replacement I1122V.

(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

CEA

(Venderova et al., 2009)

Modifiers Based on Experimental Evidence ( 0 )

Disease

Interaction

References

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.Ile1122Val

(FlyBase curators, 2019-)

Variants Synonym(s)

Associated human disease model(s)

Parkinson disease 8

External database links

ClinVar: LRRK2_1939

Comments concerning this variant

Phenotypic Data

Phenotypic Class

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)

chemical sensitive, with Scer\GAL4^da.G32

(Venderova et al., 2009)

visible, with Scer\GAL4^GMR.PF

(Venderova et al., 2009)

Phenotype Manifest In

dopaminergic neuron, with Scer\GAL4^ple.PF

(Venderova et al., 2009)

dopaminergic PPL1 neuron, with Scer\GAL4^ple.PF

(Venderova et al., 2009)

eye, with Scer\GAL4^GMR.PF

(Venderova et al., 2009)

ommatidium, with Scer\GAL4^GMR.PF

(Venderova et al., 2009)

pigment cell, with Scer\GAL4^GMR.PF

(Venderova et al., 2009)

Detailed Description

Statement

Reference

Expression of Hsap\LRRK2^{I1122V.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, compared to controls.

(Linhart et al., 2014)

Flies expressing Hsap\LRRK2^{I1122V.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)

50 day old adults expressing Hsap\LRRK2^{I1122V.Scer\UAS} under the control of Scer\GAL4^ple.PF at room temperature show loss of dopaminergic neurons 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^{I1122V.Scer\UAS} under the control of Scer\GAL4^ple.PF at 29[o]C.

Expression of Hsap\LRRK2^{I1122V.Scer\UAS} under the control of either Scer\GAL4^da.G32 or Scer\GAL4^elav.PU at room temperature or under the control of Scer\GAL4^elav.PU at 29[o]C has no significant effect on basal lifespan.

Flies expressing Hsap\LRRK2^{I1122V.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^{I1122V.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^{I1122V.Scer\UAS} under the control of Scer\GAL4^GMR.PF at 29[o]C show loss of pigmentation in the eyes. 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

Suppressed by

Statement

Reference

Hsap\LRRK2^I1122V.UAS, Scer\GAL4^Ddc.PU has abnormal locomotor behavior | adult stage phenotype, suppressible by Vps35^EY14200, Scer\GAL4^Ddc.PU

(Linhart et al., 2014)

NOT suppressed by

Statement

Reference

Hsap\LRRK2^I1122V.UAS, Scer\GAL4^GMR.PF has visible phenotype, non-suppressible by Hsap\PINK1^UAS.cYa, Scer\GAL4^GMR.PF

(Venderova et al., 2009)

NOT Suppressor of

Statement

Reference

Hsap\LRRK2^I1122V.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 suppressed by

Statement

Reference

Hsap\LRRK2^I1122V.UAS, Scer\GAL4^GMR.PF has pigment cell phenotype, non-suppressible by Hsap\PINK1^UAS.cYa, Scer\GAL4^GMR.PF

(Venderova et al., 2009)

Hsap\LRRK2^I1122V.UAS, Scer\GAL4^GMR.PF has eye phenotype, non-suppressible by Hsap\PINK1^UAS.cYa, Scer\GAL4^GMR.PF

(Venderova et al., 2009)

Enhancer of

Statement

Reference

Hsap\LRRK2^I1122V.UAS, Scer\GAL4^GMR.PF is an enhancer of interommatidial bristle phenotype of Hsap\PINK1^UAS.cYa, Scer\GAL4^GMR.PF

(Venderova et al., 2009)

NOT Suppressor of

Statement

Reference

Hsap\LRRK2^I1122V.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 Vps35^EY14200 significantly suppresses locomotor deficits in flies with expression of Hsap\LRRK2^{I1122V.Scer\UAS} driven by Scer\GAL4^Ddc.PU.

(Linhart et al., 2014)

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^{I1122V.Scer\UAS} under the control of Scer\GAL4^GMR.PF at 29[o]C. The loss of interommatidial bristles that is seen in flies expressing Hsap\PINK1^Scer\UAS.cYa under the control of Scer\GAL4^GMR.PF at 29[o]C is enhanced by co-expression of Hsap\LRRK2^{I1122V.Scer\UAS}.

(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^{I1122V.Scer\UAS}

Hsap\LRRK2^I1122V.UAS

Name Synonyms

Secondary FlyBase IDs

References (5)

Report Sections

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