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| In response to numerous reports questioning the hypokinetic phenotype of this strain, The Jackson Laboratory initiated behavioral testing on a cohort of 12 month old hemizygous FVB/N-Tg(LRRK2*R1441G)135Cjli/J and age matched controls. To date, we have been unable to validate the hypokinetic motor deficits reported for this strain. We have verified the transgene is expressed.
Mice hemizygous for the BAC LRRK2 (R1441G) transgene express a mutant form of human leucine-rich repeat kinase 2 (LRRK2*R1441G) associated with autosomal dominant, late-onset Parkinson's disease directed by the endogenous LRRK2 promoter/enhancer regions on the BAC transgene. These LRRK2R1441G mice recapitulate the motor behavioral, neurochemical, and histopathological features of Parkinson's disease and represent a robust in vivo model for studying the Parkinson's disease pathogenesis and neurodegeneration elicited by the dominant toxic effects of mutant LRRK2R1441G expression. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Noncarrier x Hemizygote (Female x Male) 22-SEP-09 Species laboratory mouse Generation N?+N3F1 (16-OCT-12)
Generation DefinitionsDonating Investigator Chenjian Li, Mount Sinai School of Medicine Description
Mice hemizygous for the BAC LRRK2R1441G transgene are viable and fertile, with expression of a mutant form of human leucine-rich repeat kinase 2 (LRRK2*R1441G) associated with autosomal dominant, late-onset Parkinson's disease directed by the endogenous LRRK2 promoter/enhancer regions on the BAC transgene. LRRK2R1441G mice from founder line RP135 express the mutant protein in cortex, cerebellum, striatum and ventral midbrain at an approximately five- to ten-fold greater level than endogenous mouse Lrrk2. LRRK2R1441G mice exhibit multiple late-onset and progressive characteristics of Parkinson's disease; including hypokinetic motor deficits (reversible with administration of levodopa or apomorphine [a direct-acting dopamine agonist]), progressive dopaminergic neuron dysfunction and degeneration, axon injury pathology, and hyperphosphorylated tau. These LRRK2R1441G mice recapitulate the motor behavioral, neurochemical, and histopathological features of Parkinson's disease and represent a robust in vivo model for studying the Parkinson's disease pathogenesis and neurodegeneration elicited by the dominant toxic effects of mutant LRRK2R1441G expression.
In an effort to better characterize LRRK2 mouse models of Parkinson's Disease, The Michael J. Fox Foundation (MJFF) initiated a longitudinal phenotyping study comparing wild type, hemizygous LRRK2 WT, and hemizygous LRRK2 R1441G animals. Similar to reports received by The Jackson Laboratory, MJFF did not observe significant differences in hemizygous FVB/N-Tg(LRRK2*R1441G)135Cjli/J compared to controls with respect to open field behaviors when tested at 8 or 12 months of age. The MJFF study did verify a weight difference in hemizygous FVB/N-Tg(LRRK2*R1441G)135Cjli/J versus controls as noted in the original publication. The MJFF study also noted significant differences in striatal content of neurotransmitters when comparing transgenic mice to controls by eight months of age. A summary of this data can be found at the MJFF resources site.
Distribution of this strain was supported by the Michael J. Fox Foundation for Parkinson's Research.Development
A human bacterial artificial chromosome (BAC) library (CHORI) was used to obtain a 188 kb BAC containing the entire human LRRK2 (leucine-rich repeat kinase 2) gene with 29 kb upstream of the LRRK2 start codon and 42 kb downstream of the LRRK2 stop codon. Bioinformatics analysis predicted that no other genes are present in the BAC. This BAC was modified by targeted mutation of the LRRK2 locus to harbor the LRRK2 R1441G (4321C>G) mutation associated with autosomal dominant, late-onset Parkinson's disease originally identified in Spanish families originating from the Basque region. This modified BAC was microinjected into fertilized FVB/NTac zygotes. BAC LRRK2R1441G mice from founder line TG-RP135 were subsequently maintained by breeding transgenic mice with FVB/N inbred mice for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to FVB/NJ inbred mice (Stock No. 001800) for at least one generation to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| 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 016575 B6;C3-Tg(PDGFB-LRRK2*G2019S)340Djmo/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 012441 STOCK Tg(tetO-LRRK2*G2019S)E3Cai/J 012449 STOCK Tg(teto-LRRK2)C7874Cai/J
Additional Web Information
Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.
Phenotype
Phenotype Information
- Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.
Parkinson Disease 8, Autosomal Dominant; PARK8
assigned by genotype
Tg(LRRK2*R1441G)135Cjli/0
FVB-Tg(LRRK2*R1441G)135Cjli
- behavior/neurological phenotype
- abnormal locomotor activation
- reduced mobility and immobility in severely affected animals are reversed by administration of levodopa and apomorphine (MGI Ref ID J:149135)
- nervous system phenotype
- *normal* nervous system phenotype
- no observable cell death or gliosis is observed in the spinal cord, and no abnormalities in general brain structure are observed in 10-12 month old mice (MGI Ref ID J:149135)
- abnormal axon morphology
- in striatum and piriform cortex, dopaminergic axons appear to be beaded or fragmented and exhibit spheroids and dystrophic neurites (MGI Ref ID J:149135)
- abnormal dopaminergic neuron morphology
- while neurons in the substantia nigra pars compacta (SNpc) and ventral tegmental area are normal in number and anatomical organization, SNpc neurons have reduced cell body sized and marked reduction in number of dendrites in the substantia nigra pars reticulata (MGI Ref ID J:149135)
- decreased dopamine level
- in striatum, levels of dopamine are reduced significantly (MGI Ref ID J:149135)
- tau protein deposits
- phosphorylated tau appears to be localized in abnormal axonal swellings and dystrophic neurites in the dorsal striatum (MGI Ref ID J:149135)
- homeostasis/metabolism phenotype
- decreased dopamine level
- in striatum, levels of dopamine are reduced significantly (MGI Ref ID J:149135)
Tg(LRRK2*R1441G)135Cjli/0
FVB/N-Tg(LRRK2*R1441G)135Cjli/J
- cellular phenotype
- abnormal autophagy
- chaperone-mediated autophagy is impaired in primary neuronal cultures as determined by the use of a photoactivatable fluorescent reporter to visualize movement from cytosol to lysosome (MGI Ref ID J:194153)
- nervous system phenotype
- alpha-synuclein inclusion body
- exogenous and endogenous alpha-synuclein is found associated to lysosomes in primary neuronal cultures (MGI Ref ID J:194153)
This mouse can be used to support research in many areas including:
Neurobiology Research
Ataxia (Movement) Defects
Neurodegeneration
Parkinson's Disease
LRRK2 strains
Research Tools
Neurobiology Research
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(LRRK2*R1441G)135Cjli | ||
|---|---|---|---|
| Allele Name | transgene insertion 135, Chenjian Li | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | LRRK2R1441G; TG-RP135; | ||
| Mutation Made By | Chenjian Li, Mount Sinai School of Medicine | ||
| Strain of Origin | FVB/NTac | ||
| Expressed Gene | LRRK2, leucine-rich repeat kinase 2, human | ||
| Promoter | LRRK2, leucine-rich repeat kinase 2, human | ||
| Molecular Note | A human bacterial artificial chromosome (BAC) library (CHORI) was used to obtain a 188 kb BAC containing the entire human LRRK2 (leucine-rich repeat kinase 2) gene with 29 kb upstream of the LRRK2 start codon and 42 kb downstream of the LRRK2 stop codon.Bioinformatics analysis predicted that no other genes are present in the BAC. This BAC was modified by targeted mutation of the LRRK2 locus to harbor the LRRK2 R1441G (4321C>G) mutation associated with autosomal dominant, late-onset Parkinson's disease originally identified in Spanish families originating from the Basque region. [MGI Ref ID J:149135] | ||
Genotyping
Genotyping Information
Genotyping Protocols
LRRK2*R1441G, Sanger sequencing
Tg(LRRK2) , Melt Curve Analysis
Tg(LRRK2) , Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Li Y; Liu W; Oo TF; Wang L; Tang Y; Jackson-Lewis V; Zhou C; Geghman K; Bogdanov M; Przedborski S; Beal MF; Burke RE; Li C. 2009. Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease. Nat Neurosci 12(7):826-8. [PubMed: 19503083] [MGI Ref ID J:149135]
Additional References
Tg(LRRK2*R1441G)135Cjli relatedGillardon F; Schmid R; Draheim H. 2012. Parkinson's disease-linked leucine-rich repeat kinase 2(R1441G) mutation increases proinflammatory cytokine release from activated primary microglial cells and resultant neurotoxicity. Neuroscience 208:41-8. [PubMed: 22342962] [MGI Ref ID J:184728]
Orenstein SJ; Kuo SH; Tasset I; Arias E; Koga H; Fernandez-Carasa I; Cortes E; Honig LS; Dauer W; Consiglio A; Raya A; Sulzer D; Cuervo AM. 2013. Interplay of LRRK2 with chaperone-mediated autophagy. Nat Neurosci 16(4):394-406. [PubMed: 23455607] [MGI Ref ID J:194153]
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 siblings or to FVB/NJ inbred mice (Stock No. 001800). Mating System Noncarrier x Hemizygote (Female x Male) 22-SEP-09 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(LRRK2*R1441G)135Cjli
Price per Pair (US dollars $) Pair Genotype $296.00 Hemizygous for Tg(LRRK2*R1441G)135Cjli x Noncarrier $296.00 Noncarrier x Hemizygous for Tg(LRRK2*R1441G)135Cjli 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(LRRK2*R1441G)135Cjli
Price per Pair (US dollars $) Pair Genotype $384.80 Hemizygous for Tg(LRRK2*R1441G)135Cjli x Noncarrier $384.80 Noncarrier x Hemizygous for Tg(LRRK2*R1441G)135Cjli 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 | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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