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| G2019S-LRRK2 transgenic mice have a minimal cytomegalovirus (CMV) enhancer and human platelet derived growth factor, B polypeptide (PDGFB) promoter/enhancer elements driving expression of a mutated full length human leucine-rich repeat kinase 2 (LRRK2*G2019S) cDNA. These mice may be useful for studying Parkinson's Disease pathogenesis and neurodegeneration elicited by the dominant toxic effects of mutant LRRK2*G2019S expression. | |||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Type Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Noncarrier x Hemizygote (Female x Male) 19-OCT-11 Mating System Hemizygote x Noncarrier (Female x Male) 19-OCT-11 Species laboratory mouse Generation N5+F1 (08-MAR-12)
Generation DefinitionsDonating Investigator Valina Dawson, The Johns Hopkins University Donating Investigator Darren J Moore, Ecole Polytechnique Federale de Lausanne Description
G2019S-LRRK2 transgenic mice have a minimal cytomegalovirus (CMV) enhancer and human platelet derived growth factor, B polypeptide (PDGFB) promoter/enhancer elements driving expression of a mutated full length human leucine-rich repeat kinase 2 (LRRK2*G2019S) cDNA. Hemizygotes are viable, fertile, and normal in size. The LRRK2 cDNA was modified to harbor the LRRK2*G2019S mutation associated with autosomal dominant, late-onset Parkinson's Disease (PD) originally identified in multiple Spanish families and patients with PD. LRRK2 protein, also known as Dardarin, contains multiple functional domains and may play a role in regulating alpha-synuclein-mediated neuropathology through modulating the intracellular trafficking and accumulation of SNCA protein. G2019S-LRRK2 is expressed throughout the olfactory bulb, cerebral cortex, hippocampus, striatum, cerebellum, and neurons of the substantia nigra pars compacta. G2019S-LRRK2 is also overexpressed (2.7-fold over endogenous) within tyrosine hydroxylase (TH)-positive dopaminergic neurons of the substantia nigra pars compacta. These transgenic mice display progressive nigral dopaminergic degeneration, in addition to reduced complexity of cultured midbrain dopaminergic neurons. They also exhibit enhanced dopamine turnover in the olfactory bulb, as well as autophagic and mitochondrial abnormalities throughout the brain. These mice may be useful for studying PD pathogenesis and neurodegeneration elicited by the dominant toxic effects of mutant LRRK2*G2019S expression.Development
The G2019S-LRRK2 transgene was designed with a minimal cytomegalovirus (CMV) enhnacer and human platelet derived growth factor, B polypeptide (PDGFB) promoter/enhancer elements driving expression of a full length human leucine-rich repeat kinase 2 (LRRK2) cDNA. LRRK2 cDNA was modified to harbor the LRRK2*G2019S mutation associated with autosomal dominant, late-onset Parkinson's disease. This transgene was microinjected into fertilized (C57BL/6J x C3H/HeJ) F1 oocytes. LRRK2*G2019S mice from founder line 340 were bred to C57BL/6J mice for at least 3 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J mice (Stock No. 000664) for at least one generation to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
Related Strains
Parkinson's Disease Models
View Parkinson's Disease Models (109 strains)
013583 B6.Cg-Tg(tetO-LRRK2)C7874Cai/J 012445 B6.FVB-Tg(LRRK2)WT1Mjfa/J 012446 B6.FVB-Tg(LRRK2*G2019S)1Mjfa/J 016576 B6;C3-Tg(PDGFB-LRRK2*R1441C)574Djmo/J 013725 B6;SJL-Tg(LRRK2)66Mjff/J 009610 FVB/N-Tg(LRRK2)1Cjli/J 009609 FVB/N-Tg(LRRK2*G2019S)1Cjli/J 009604 FVB/N-Tg(LRRK2*R1441G)135Cjli/J 012441 STOCK Tg(tetO-LRRK2*G2019S)E3Cai/J 012449 STOCK Tg(teto-LRRK2)C7874Cai/J
004662 B6.Cg-Tg(PDGFB-APP)5Lms/J 006293 B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2Mmjax 018923 B6.Cg-Tg(PDGFB-MAPT*P301S)77Elan/J 016576 B6;C3-Tg(PDGFB-LRRK2*R1441C)574Djmo/J 008073 FVB-Tg(PDGFB-Adra2b)13Hag/J
Additional Web Information
Use of MICE by companies or for-profit entities requires a license prior to shipping.
Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.
Phenotype
Phenotype Information
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Parkinson Disease 8, Autosomal Dominant; PARK8 (LRRK2)
assigned by genotype
Tg(PDGFB-LRRK2*G2019S)340Djmo/0
involves: C3H/HeJ * C57BL/6J
- nervous system phenotype
- abnormal neuron morphology
- neuronal soma from the cerebral cortex and striatum of 17-18 month old mice exhibit condensed aggregated mitochondria, damaged mitochondria and an increase in the density of autophagic vacuoles (MGI Ref ID J:171645)
- abnormal neurite morphology
- abnormal axon morphology
- axonal processes from the cerebral cortex and striatum of 17-18 month old mice contain an increase in the density of autophagic vacuoles (MGI Ref ID J:171645)
- decreased dopaminergic neuron number
- by 19-21 months, transgenic mice exhibit an 18% loss of TH+ dopaminergic neurons and a 17% loss of Nissl+ nigral neurons in the substantia nigra pars compacta (MGI Ref ID J:171645)
- dopaminergic neuritic density is reduced by 14% in substantia nigra pars reticulata, but not in the striatum (MGI Ref ID J:171645)
- normal numbers of dopaminergic neurons are observed in the ventral tegemental area (MGI Ref ID J:171645)
- homeostasis/metabolism phenotype
- abnormal homeostasis
- dopamine turnover is increased in 14-15 month old mice (MGI Ref ID J:171645)
- levels of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), are decreased in the olfactory bulb at 14-15 months of age, however, dopamine levels are not increased (MGI Ref ID J:171645)
- increased serotonin level
- mice exhibit a small, but significant, increase in serotonin levels (MGI Ref ID J:171645)
- cellular phenotype
- abnormal autophagy
- observed in the brain of aged mice (MGI Ref ID J:171645)
This mouse can be used to support research in many areas including:
Neurobiology Research
Neurodegeneration
Parkinson's Disease
LRRK2 strains
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(PDGFB-LRRK2*G2019S)340Djmo | ||
|---|---|---|---|
| Allele Name | transgene insertion 340, Darren Moore | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | G2019S-LRRK2; | ||
| Mutation Made By | Darren Moore, Ecole Polytechnique Federale de Lausanne | ||
| Strain of Origin | (C57BL/6J x C3H/HeJ)F1 | ||
| Expressed Gene | LRRK2, leucine-rich repeat kinase 2, human | ||
| Promoter | PDGFB, platelet-derived growth factor beta polypeptide, human | ||
| Molecular Note | The G2019S-LRRK2 transgene was designed with a minimal cytomegalovirus (CMV) enhancer and human platelet derived growth factor, B polypeptide (PDGFB) promoter/enhancer elements driving expression of a full length human leucine-rich repeat kinase 2 (LRRK2) cDNA. LRRK2 cDNA was modified by targeted mutation of the LRRK2 locus to harbor the LRRK2*G2019S mutation associated with autosomal dominant, late-onset Parkinson's disease. Line 340 was generated. [MGI Ref ID J:171645] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(PDGFB-LRRK2), Melt Curve Analysis
Tg(PDGFB-LRRK2), Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Ramonet D; Daher JP; Lin BM; Stafa K; Kim J; Banerjee R; Westerlund M; Pletnikova O; Glauser L; Yang L; Liu Y; Swing DA; Beal MF; Troncoso JC; McCaffery JM; Jenkins NA; Copeland NG; Galter D; Thomas B; Lee MK; Dawson TM; Dawson VL; Moore DJ. 2011. Dopaminergic Neuronal Loss, Reduced Neurite Complexity and Autophagic Abnormalities in Transgenic Mice Expressing G2019S Mutant LRRK2. PLoS One 6(4):e18568. [PubMed: 21494637] [MGI Ref ID J:171645]
Additional References
Tg(PDGFB-LRRK2*G2019S)340Djmo relatedDaher JP; Pletnikova O; Biskup S; Musso A; Gellhaar S; Galter D; Troncoso JC; Lee MK; Dawson TM; Dawson VL; Moore DJ. 2012. Neurodegenerative phenotypes in an A53T alpha-synuclein transgenic mouse model are independent of LRRK2. Hum Mol Genet 21(11):2420-31. [PubMed: 22357653] [MGI Ref ID J:183780]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygous mice may be bred to wildtype (noncarrier) mice from the colony. Mating System Noncarrier x Hemizygote (Female x Male) 19-OCT-11 Hemizygote x Noncarrier (Female x Male) 19-OCT-11 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Hemizygous for Tg(PDGFB-LRRK2*G2019S)340Djmo
Price per Pair (US dollars $) Pair Genotype $296.00 Hemizygous for Tg(PDGFB-LRRK2*G2019S)340Djmo x Noncarrier $296.00 Noncarrier x Hemizygous for Tg(PDGFB-LRRK2*G2019S)340Djmo Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Hemizygous for Tg(PDGFB-LRRK2*G2019S)340Djmo
Price per Pair (US dollars $) Pair Genotype $384.80 Hemizygous for Tg(PDGFB-LRRK2*G2019S)340Djmo x Noncarrier $384.80 Noncarrier x Hemizygous for Tg(PDGFB-LRRK2*G2019S)340Djmo Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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