| |||||||||||||||||||
| R1441C-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*R1441C) cDNA. These mice may be useful for studying Parkinson's disease pathogenesis and neurodegeneration elicited by the dominant toxic effects of mutant LRRK2*R1441G expression. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Type Mutant Stock; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Hemizygote x Noncarrier (Female x Male) 31-AUG-11 Species laboratory mouse Generation F?+ (25-MAY-11)
Generation DefinitionsDonating Investigator Valina Dawson, The Johns Hopkins University Donating Investigator Darren J Moore, Ecole Polytechnique Federale de Lausanne Description
R1441C-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*R1441C) cDNA. Hemizygotes are viable, fertile, and normal in size. The LRRK2 cDNA was modified to harbor the LRRK2*R1441C mutation associated with autosomal dominant, late-onset Parkinson's disease originally identified in family D from Western Nebraska. 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. R1441C-LRRK2 is selectively overexpressed in the cerebral cortex and cerebellum. These mice display reduced levels of cortical catecholamines, a progressive impairment of locomotor activity and the accumulation of autophagic vacuoles in the cerebral cortex. These mice may be useful for studying Parkinson's disease pathogenesis and neurodegeneration elicited by the dominant toxic effects of mutant LRRK2*R1441C expression.Development
The R1441C-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 full length human leucine-rich repeat kinase 2 (LRRK2) CDNA. LRRK2 cDNA was modified to harbor the LRRK2*R1441C mutation associated with autosomal dominant, late-onset Parkinson's disease. This transgene was microinjected into fertilized (C57BL/6J x C3H/HeJ) F1 oocytes. LRRK2*R1441C mice from founder line 574 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 016575 B6;C3-Tg(PDGFB-LRRK2*G2019S)340Djmo/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 016575 B6;C3-Tg(PDGFB-LRRK2*G2019S)340Djmo/J 008073 FVB-Tg(PDGFB-Adra2b)13Hag/J
Additional Web Information
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*R1441C)574Djmo/0
involves: C3H/HeJ * C57BL/6J
- behavior/neurological phenotype
- decreased vertical activity
- reduction in vertical locomotor activity by 15 months of age (MGI Ref ID J:171645)
- hypoactivity
- reduction in horizonal locomotor activity by 15 months of age (MGI Ref ID J:171645)
- nervous system phenotype
- abnormal neuron morphology
- neuronal soma from the cerebral cortex and striatum of 20-23 month old mice exhibit condensed aggregated mitochondria, damaged mitochondria and an increase in the density of autophagic vacuoles (MGI Ref ID J:171645)
- decreased dopamine level
- decrease in cortical dopamine levels (MGI Ref ID J:171645)
- homeostasis/metabolism phenotype
- decreased circulating noradrenaline level
- decrease in cortical norepinephrine levels (MGI Ref ID J:171645)
- decreased dopamine level
- decrease in cortical dopamine levels (MGI Ref ID J:171645)
- cellular phenotype
- abnormal autophagy
- observed in the brains 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*R1441C)574Djmo | ||
|---|---|---|---|
| Allele Name | transgene insertion 574, Darren Moore | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | R1441C-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 R1441C-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 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*R1441C mutation associated with autosomal dominant, late-onset Parkinson's disease. Line 574 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]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygous mice may be bred to wildtype (noncarrier) mice from the colony. Mating System Hemizygote x Noncarrier (Female x Male) 31-AUG-11
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*R1441C)574Djmo
Price per Pair (US dollars $) Pair Genotype $296.00 Hemizygous for Tg(PDGFB-LRRK2*R1441C)574Djmo x Noncarrier 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*R1441C)574Djmo
Price per Pair (US dollars $) Pair Genotype $384.80 Hemizygous for Tg(PDGFB-LRRK2*R1441C)574Djmo x Noncarrier 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.
|
|
|
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.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Payment Terms and Conditions
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
See Terms of Use tab for General Terms and Conditions
The Jackson Laboratory's Genotype Promise
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering Information
JAX® Mice
Surgical and Preconditioning Services
JAX® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form
Terms of Use
Terms of Use
General Terms and Conditions
For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
Contact information
General inquiries regarding Terms of UseContracts Administration
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
JAX® Mice, Products & Services Conditions of Use
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.
No Liability
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.