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WormBase Tree Display for Transgene: WBTransgene00008742

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Name Class

WBTransgene00008742Public_namecwrIs722
Summary[Pdat-1::GFP; Pdat-1::LRRK2(WT); lin-15(+)]
SynonymLRRK2+
ConstructionConstructWBCnstr00008442
Coinjection_otherlin-15(+)
Integration_methodUV
Construction_summaryHuman cDNA encoding full-length C-terminally FLAG-tagged human LRRK2 WT was previously constructed in pCEP4 vector as described (Guo et al., 2007). The Pdat-1 promoter sequence was PCR amplified from the upstream 719-bp region containing the initiation codon ATG using the corresponding Promoterome clone (Geneservice, UK) as the template. The plasmid pFXneEGFP used previously as a C. elegans expression vector (Kuwahara et al., 2006) was modified by switching the original BamHI site to the region 17-bp downstream of the NotI site. The PCR product of Pdat-1 was subsequently inserted into KpnI and HindIII sites immediately upstream of the enhanced green fluorescent protein (GFP) of the modified pFXneEGFP to create Pdat-1::GFP (serving as a fluorescent reporter for DA neurons). The FLAG-tagged human LRRK2 cDNA was excised from NotI and BamHI sites of pCEP4 and subcloned into the same sites in the Pdat-1-containing pFXneEGFP, generating Pdat-1::LRRK2.
Genetic_informationIntegrated
PhenotypeWBPhenotype:0000234Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
RemarkAnimals exhibited a significant decrease in dopamine levels in an age-dependent manner as no apparent changes in dopamine levels from control animals were observed on adult day 0.Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
Caused_by_otherLRRK2(WT)Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
EQ_annotationsAnatomy_termWBbt:0005278PATO:0000460Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
WBbt:0005244PATO:0000460Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
WBPhenotype:0000636Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
RemarkTransgenic worms overexpressing LRRK2 WT, R1441C or G2019S in DA neurons manifested adult-onset and age-dependent neurodegeneration characterized by the loss of DA neuron soma and breakdown of neurites as compared to the GFP control line, although no overt morphological changes within the DA neurons were observed before animals reached adulthood.Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
Caused_by_otherLRRK2(WT)Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
EQ_annotationsAnatomy_termWBbt:0005278PATO:0000460Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
WBbt:0005244PATO:0000460Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
WBPhenotype:0000642Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
RemarkLRRK2 overexpression led to an adult-onset dysfunction in locomotion. Control worms showed similar motility at the beginning of adulthood (adult day 0). However, LRRK2 overexpressing lines manifested abnormally hyperactive locomotion from adult day 2 (young) through day 8 (old) as compared to the GFP reporter line. Treatment with exogenous dopamine rescued the locomotor dysfunction.Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
Caused_by_otherLRRK2(WT)Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
EQ_annotationsAnatomy_termWBbt:0005278PATO:0000460Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
WBbt:0005244PATO:0000460Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
WBPhenotype:0004028Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
RemarkTransgenic C. elegans lines overexpressing LRRK2 WT, R1441C and G2019S showed normal behavior at the beginning of the adulthood (adult day 0), but they manifested a progressive loss of the basal slowing response from adult day 2 to day 4. This response could be rescued following feeding with exogenous dopamine.Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
Caused_by_otherLRRK2(WT)Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
EQ_annotationsAnatomy_termWBbt:0005278PATO:0000460Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
WBbt:0005244PATO:0000460Paper_evidenceWBPaper00036154
Curator_confirmedWBPerson712
ReferenceWBPaper00036154
WBPaper00051457
WBPaper00051539
SpeciesCaenorhabditis elegans