Allele Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}

General Information
Symbol	Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}	Species	H. sapiens
Name		FlyBase ID	FBal0249096
Feature type	allele	Associated gene	Hsap\LRRK2

Allele class
Mutagen	in vitro construct - regulatory fusion, in vitro construct - coding region fusion
Recent Updates
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FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Nature of the Allele
Allele class
Mutagen	in vitro construct - coding region fusion (Liu et al., 2008) in vitro construct - regulatory fusion (Liu et al., 2008)
Mutations Mapped to the Genome

Type Location Additional Notes References
Associated Sequence Data
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name

UniProtKB/Swiss-Prot
UniProtKB/TrEMBL

Progenitor genotype
Nature of the lesion	Statement Reference Scer\UAS regulatory sequences drive expression of Hsap\LRRK2 with an N-terminal T:Zzzz\FLAG-tag. (Liu et al., 2008)
Carried in construct	P{UAS-LRRK2.FLAG} (Liu et al., 2008, Gehrke et al., 2010, Lee et al., 2010, Xiong et al., 2012)
Tagged with	T:Zzzz\FLAG (Liu et al., 2008)
Cytology
Phenotypic Data
Phenotypic Class
	locomotor behavior defective, with Scer\GAL4^Ddc.PL (Liu et al., 2008) locomotor behavior defective, with Scer\GAL4^elav.PU (Liu et al., 2008) locomotor behavior defective, with Scer\GAL4^ple.PF (Xiong et al., 2012) neuroanatomy defective, with Scer\GAL4^elav.PU (Liu et al., 2008) neuroanatomy defective, with Scer\GAL4^elav-C155 (Lee et al., 2010) neuroanatomy defective, with Scer\GAL4^GMR.PF (Liu et al., 2008) neuroanatomy defective, with Scer\GAL4^Mhc.PW (Lee et al., 2010) neuroanatomy defective, with Scer\GAL4^ple.PF (Xiong et al., 2012) neurophysiology defective, with Scer\GAL4^elav-C155 (Lee et al., 2010) short lived, with Scer\GAL4^Ddc.PL (Liu et al., 2008) short lived, with Scer\GAL4^elav.PU (Liu et al., 2008)
Phenotype Manifest In
	dopaminergic neuron, with Scer\GAL4^Ddc.PL (Liu et al., 2008) dopaminergic neuron, with Scer\GAL4^elav.PU (Liu et al., 2008) dopaminergic neuron, with Scer\GAL4^ple.PF (Xiong et al., 2012) dopaminergic PAL neuron, with Scer\GAL4^ple.PF (Xiong et al., 2012) dopaminergic PPL1 neuron, with Scer\GAL4^ple.PF (Xiong et al., 2012) dopaminergic PPM1 neuron, with Scer\GAL4^ple.PF (Xiong et al., 2012) dopaminergic PPM2 neuron, with Scer\GAL4^ple.PF (Xiong et al., 2012) dopaminergic PPM3 neuron, with Scer\GAL4^ple.PF (Xiong et al., 2012) mitochondrion, with Scer\GAL4^elav-C155 (Lee et al., 2010) neuromuscular junction, with Scer\GAL4^elav-C155 (Lee et al., 2010) neuromuscular junction, with Scer\GAL4^Mhc.PW (Lee et al., 2010) retina, with Scer\GAL4^GMR.PF (Liu et al., 2008) type I bouton, with Scer\GAL4^elav-C155 (Lee et al., 2010) type I bouton, with Scer\GAL4^Mhc.PW (Lee et al., 2010)
Detailed Description
	Statement Reference Overexpression of Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] in dopaminergic neurons, under the control of Scer\GAL4[ple.PF], leads to a substantial reduction of dopamine neurons in the adult brain hemisphere. Expression of Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] under the control of Scer\GAL4[ple.PF] significantly reduces climbing ability. (Xiong et al., 2012) Overexpression of Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] pre- or post-synaptically (under the control of Scer\GAL4[elav-C155] or Scer\GAL4[Mhc.PW], respectively) results in a reduction in the total number of type I boutons on muscle 6/7 from the A3 segment. In addition, neuromuscular junction length and branch number are decreased by 25%. Separate quantification of type Ib versus type Is boutons on muscle 6/7 reveals a similar degree (20%) of decrease in the number of each type of bouton. The neuromuscular junction morphology phenotype caused by overexpression of Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] by Scer\GAL4[Mhc.PW] is rescued by rapamycin treatment. Scer\GAL4[Mhc.PW]-driven expression of Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] does not affect neuromuscular junction MT cytoskeleton formation. Newly synthesized tubulin inside synaptic boutons is more fragmented in animals expressing Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] presynaptically (under the control of Scer\GAL4[elav-C155]). Neuronal overexpression of Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] (under the control of Scer\GAL4[elav-C155]) leads to a decrease of mitochondria number in terminal boutons and a significant increase of mEJC frequency. Quantal content is not significantly changed in these animals compared to controls. (Lee et al., 2010) Expression of Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] under the control of Scer\GAL4[GMR.PF] results in retinal degeneration by 3 weeks after eclosion. Expression of Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] driven by Scer\GAL4[Ddc.PL] causes early mortality and locomotion impairment. Expression of Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] under the control of Scer\GAL4[Ddc.PL] leads to selective loss of dopaminergic neurons. Expression of Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] driven by Scer\GAL4[elav.PU] causes late-onset locomotion impairment, shortened lifespan and selective loss of dopaminergic neurons. (Liu et al., 2008)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressed by
Statement Reference Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^ple.PF has locomotor behavior defective phenotype, suppressible by Hsap\ARFGAP1^{Scer\UAS.T:Ivir\HA1}, Scer\GAL4^ple.PF (Xiong et al., 2012) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^ple.PF has locomotor behavior defective phenotype, suppressible by Hsap\ARFGAP1^{Δ64.Scer\UAS.T:Ivir\HA1}, Scer\GAL4^ple.PF (Xiong et al., 2012) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^ple.PF has neuroanatomy defective phenotype, suppressible by Hsap\ARFGAP1^{Scer\UAS.T:Ivir\HA1}, Scer\GAL4^ple.PF (Xiong et al., 2012) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^ple.PF has neuroanatomy defective phenotype, suppressible by Hsap\ARFGAP1^{Δ64.Scer\UAS.T:Ivir\HA1}, Scer\GAL4^ple.PF (Xiong et al., 2012)
Phenotype Manifest In
Suppressed by
Statement Reference Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^elav-C155 has mitochondrion phenotype, suppressible by futsch^EP1419, Scer\GAL4^elav-C155 (Lee et al., 2010) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^elav-C155 has neuromuscular junction phenotype, suppressible by futsch^EP1419, Scer\GAL4^elav-C155 (Lee et al., 2010) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^elav-C155 has type I bouton phenotype, suppressible by futsch^EP1419, Scer\GAL4^elav-C155 (Lee et al., 2010) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^ple.PF has dopaminergic PAL neuron phenotype, suppressible by Hsap\ARFGAP1^{Scer\UAS.T:Ivir\HA1}, Scer\GAL4^ple.PF (Xiong et al., 2012) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^ple.PF has dopaminergic PPM1 neuron phenotype, suppressible by Hsap\ARFGAP1^{Scer\UAS.T:Ivir\HA1}, Scer\GAL4^ple.PF (Xiong et al., 2012) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^ple.PF has dopaminergic PPM1 neuron phenotype, suppressible by Hsap\ARFGAP1^{Δ64.Scer\UAS.T:Ivir\HA1}, Scer\GAL4^ple.PF (Xiong et al., 2012) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^ple.PF has dopaminergic PPM2 neuron phenotype, suppressible by Hsap\ARFGAP1^{Scer\UAS.T:Ivir\HA1}, Scer\GAL4^ple.PF (Xiong et al., 2012) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^ple.PF has dopaminergic PPM2 neuron phenotype, suppressible by Hsap\ARFGAP1^{Δ64.Scer\UAS.T:Ivir\HA1}, Scer\GAL4^ple.PF (Xiong et al., 2012)
NOT suppressed by
Statement Reference Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^Mhc.PW has neuromuscular junction phenotype, non-suppressible by futsch^EP1419, Scer\GAL4^Mhc.PW (Lee et al., 2010) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^Mhc.PW has type I bouton phenotype, non-suppressible by futsch^EP1419, Scer\GAL4^Mhc.PW (Lee et al., 2010) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^ple.PF has dopaminergic PAL neuron phenotype, non-suppressible by Hsap\ARFGAP1^{Δ64.Scer\UAS.T:Ivir\HA1}, Scer\GAL4^ple.PF (Xiong et al., 2012) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^ple.PF has dopaminergic PPL1 neuron phenotype, non-suppressible by Hsap\ARFGAP1^{Scer\UAS.T:Ivir\HA1}, Scer\GAL4^ple.PF (Xiong et al., 2012) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^ple.PF has dopaminergic PPL1 neuron phenotype, non-suppressible by Hsap\ARFGAP1^{Δ64.Scer\UAS.T:Ivir\HA1}, Scer\GAL4^ple.PF (Xiong et al., 2012) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^ple.PF has dopaminergic PPM3 neuron phenotype, non-suppressible by Hsap\ARFGAP1^{Scer\UAS.T:Ivir\HA1}, Scer\GAL4^ple.PF (Xiong et al., 2012) Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^ple.PF has dopaminergic PPM3 neuron phenotype, non-suppressible by Hsap\ARFGAP1^{Δ64.Scer\UAS.T:Ivir\HA1}, Scer\GAL4^ple.PF (Xiong et al., 2012)
Suppressor of
Statement Reference Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}, Scer\GAL4^GMR.PF is a suppressor of eye phenotype of Hsap\ARFGAP1^{Scer\UAS.T:Ivir\HA1}, Scer\GAL4^GMR.PF (Xiong et al., 2012)
Additional Comments
Genetic Interactions
Statement Reference
Xenogenetic Interactions
Statement Reference Co-expression of Hsap\ARFGAP1[Scer\UAS.T:Ivir\HA1] with Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] in dopaminergic neurons, under the control of Scer\GAL4[ple.PF], significantly prevents the loss of dopamine neurons in PAL and PPM1/2 but not PPM3 or PPL1 clusters. Co-expression of Hsap\ARFGAP1[Δ64.Scer\UAS.T:Ivir\HA1] with Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] in dopaminergic neurons, under the control of Scer\GAL4[ple.PF], rescues dopaminergic neuronal loss in the PPM1/2 but does not significantly rescue in the other dopaminergic clusters. Co-expression of either Hsap\ARFGAP1[Scer\UAS.T:Ivir\HA1] or Hsap\ARFGAP1[Δ64.Scer\UAS.T:Ivir\HA1] in dopaminergic neurons, under the control of Scer\GAL4[ple.PF], rescues the climbing defect seen in Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG]-expressing flies. Co-expression of Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] rescues the eye defects seen upon expression of Hsap\ARFGAP1[Scer\UAS.T:Ivir\HA1] under the control of Scer\GAL4[GMR.PF]. (Xiong et al., 2012) Co-expression of futsch[EP1419] pre-synaptically rescues the synaptic overgrowth phenotype found upon expression of Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] pre-synaptically under the control of Scer\GAL4[elav-C155]. However, synaptic defects caused by post-synaptic expression of Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] are not suppressed when futsch[EP1419] is expressed post-synaptically (under the control of Scer\GAL4[Mhc.PW]). The abnormal microtubule phenotype seen upon Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] presynaptic expression is rescued by a futsch[EP1419] expression (both under the control of Scer\GAL4[elav-C155]). Neuronal co-expression of futsch[EP1419] with Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] rescues the mitochondrial distribution phenotype seen upon Hsap\LRRK2[Scer\UAS.T:Zzzz\FLAG] expression alone. (Lee et al., 2010)
Complementation & Rescue Data
Comments
Stocks ( 0 )

Notes on Origin
Discoverer

External Crossreferences & Linkouts
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Linkouts

Synonyms & Secondary IDs ( 1 )
Reported As
Symbol Synonym	Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}
Name Synonym
Secondary FlyBase IDs

References ( 4 )
Research paper	Xiong et al., 2012, J. Neurosci. 32(11): 3877--3886 ArfGAP1 Is a GTPase Activating Protein for LRRK2: Reciprocal Regulation of ArfGAP1 by LRRK2. [FBrf0217819] Gehrke et al., 2010, Nature 466(7306): 637--641 Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. [FBrf0211387] Lee et al., 2010, J. Neurosci. 30(50): 16959--16969 LRRK2 kinase regulates synaptic morphology through distinct substrates at the presynaptic and postsynaptic compartments of the Drosophila neuromuscular junction. [FBrf0212570] Liu et al., 2008, Proc. Natl. Acad. Sci. U.S.A. 105(7): 2693--2698 A Drosophila model for LRRK2-linked parkinsonism. [FBrf0204181]

Allele Hsap\LRRK2Scer\UAS.T:Zzzz\FLAG

Allele Hsap\LRRK2^{Scer\UAS.T:Zzzz\FLAG}