| 
| ||||||||||||||||||
| Mice homozygous for the LRRK2 R1441C knockin (R1441C KI) express the R1441C mutant form of leucine-rich repeat kinase 2 (Lrrk2) associated with Parkinson's disease. These LRRK2 R1441C KI mice may be useful in studying abnormal regulation of activity-dependent dopamine neurotransmission and D2 receptor-mediated function, which may represent pathogenic precursors preceding dopaminergic degeneration in Parkinson's disease. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?pN1
Generation DefinitionsDonating Investigator Jie Shen, Harvard Med Sch/Brigham Women's Hosp Description
Mice homozygous for the LRRK2 R1441C knockin (R1441C KI) allele are viable and fertile, with expression of the R1441C mutant form of leucine-rich repeat kinase 2 (Lrrk2) associated with Parkinson's disease. Homozygous LRRK2 R1441C KI mice appear grossly normal and exhibit no spontaneous dopaminergic neurodegeneration or alterations in steady-state levels of striatal dopamine up to two years of age. Homozygous mice have significantly impaired dopaminergic transmission and impaired dopamine D2 receptor-mediated function. Specifically, homozygotes show reduced psychostimulant (amphetamine)-induced locomotor activity and reduced sensitivity to D2 receptor agonist (quinpirole)-induced locomotor inhibition. Also, nigral neurons from homozygous acute horizontal midbrain slices exhibit decreased sensitivity to inhibition of firing induced by dopamine, quinpirole, and amphetamine. Chromaffin cells cultured from homozygous mice also show compromised potassium-stimulated exocytotic catecholamine release.Development
A targeting vector was designed to insert the Parkinson's disease-associated R1441C missense mutation into the highly conserved GTPase domain in exon 31 (as well as a loxP-flanked PGK-neo cassette downstream of exon 31) of the Lrrk2 (leucine-rich repeat kinase 2) locus. This construct was electroporated into (C57BL/6 x 129)F1-derived MKV6.5 embryonic stem (ES) cells. Correctly targeted ES cells were then transiently transfected with a Cre recombinase-expressing plasmid to remove the PGK-neo cassette. The resulting ES cells with the LRRK2 R1441C knockin (and a single loxP site downstream of exon 31) were injected into recipient blastocysts. Chimeric mice were bred with B6/129 F1 mice to generate the mutant colony. Heterozygous mice were bred together for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred with B6129SF1/J hybrid mice (Stock No. 101043) for at least one generation to establish the colony.
Control Information
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Parkinson's Disease Models
View Parkinson's Disease Models (109 strains)
009346 B6.Cg-Lrrk2tm1.1Shn/J
012453 B6.129X1(FVB)-Lrrk2tm1.1Cai/J 012466 B6.Cg-Tg(Lrrk2)6Yue/J 012467 B6.Cg-Tg(Lrrk2*G2019S)2Yue/J 016209 B6;129-Lrrk2tm2.1Shn/J 016210 B6;129-Lrrk2tm3.1Shn/J 012444 C57BL/6-Lrrk2tm1Mjfa/J 016122 C57BL/6N-Lrrk1tm1.1Mjff Lrrk2tm1.1Mjff/J 016121 C57BL/6N-Lrrk2tm1.1Mjff/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 gene homology relationships. Phenotypic similarity to the human disease has not been tested. Parkinson Disease 8, Autosomal Dominant; PARK8 (LRRK2)
assigned by genotype
Lrrk2tm1.1Shn/Lrrk2tm1.1Shn
involves: 129 * C57BL/6
- nervous system phenotype
- *normal* nervous system phenotype
- mice exhibit normal dopaminergic neurons and striatal catecholamine levels (MGI Ref ID J:151944)
- abnormal action potential
- the response of nigral neurons to dopamine treatment exhibits a smaller amplitude and shorter duration of hyperpolarization than in similarly treated wild-type cells (MGI Ref ID J:151944)
- dopamine-treated nigral neurons exhibit a shorter time to predrug firing activity compared with similarly treated wild-type neurons (MGI Ref ID J:151944)
- quinpirole-treated nigral neurons are less sensitive than similarly treated wild-type neurons (MGI Ref ID J:151944)
- amphetamine-treated neurons exhibit a shorter cessation of firing compared with similarly treated wild-type neurons with smaller hyperpolarization (MGI Ref ID J:151944)
- homeostasis/metabolism phenotype
- abnormal response/metabolism to endogenous compounds
- the response of nigral neurons to dopamine treatment exhibits a smaller amplitude and shorter duration of hyperpolarization than in similarly treated wild-type cells (MGI Ref ID J:151944)
- dopamine-treated nigral neurons exhibit a shorter time to predrug firing activity compared with similarly treated wild-type neurons (MGI Ref ID J:151944)
- decreased physiological sensitivity to xenobiotic
- amphetamine-treated neurons exhibit a shorter cessation of firing compared with similarly treated wild-type neurons with smaller hyperpolarization (MGI Ref ID J:151944)
- behavior/neurological phenotype
- impaired behavioral response to xenobiotic
- following treatment with amphetamine, mice fail to exhibit an increase in locomotor activity unlike similarly treated wild-type mice (MGI Ref ID J:151944)
- mice treated with quinpirole do not exhibit as much of a decrease in locomotor activity (horizontal and vertical movements) as similarly treated wild-type mice (MGI Ref ID J:151944)
- quinpirole-treated nigral neurons are less sensitive than similarly treated wild-type neurons (MGI Ref ID J:151944)
- impaired behavioral response to addictive substance
- following treatment with amphetamine, mice fail to exhibit an increase in locomotor activity unlike similarly treated wild-type mice (MGI Ref ID J:151944)
- endocrine/exocrine gland phenotype
- abnormal adrenal gland secretion
- adrenal chromaffin cells exhibit reduced catecholamine release per cell, quantal size, and frequency of release events when stimulated with high potassium ion compared to similarly treated wild-type cells (MGI Ref ID J:151944)
This mouse can be used to support research in many areas including:
Neurobiology Research
Ataxia (Movement) Defects
Neurodegeneration
Parkinson's Disease
LRRK2 strains
Receptor Defects
dopamine receptor
Research Tools
Neurobiology Research
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Lrrk2tm1.1Shn | ||
|---|---|---|---|
| Allele Name | targeted mutation 1.1, Jie Shen | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | Lrrk2R1441C; | ||
| Mutation Made By | Jie Shen, Harvard Med Sch/Brigham Women's Hosp | ||
| Strain of Origin | (C57BL/6 x 129)F1 | ||
| Promoter | Lrrk2, leucine-rich repeat kinase 2, mouse, laboratory | ||
| Molecular Note | Exon 31 was replaced with one in which nucleotide substitutions led to the amino acid substitution of cysteine for arginine at position 1441 (R1441C). A floxed neo cassette was inserted downstream of the modified exon and removed by transient cre expression in ES cells. [MGI Ref ID J:151944] | ||
References
References provided by MGI
Selected Reference(s)
Tong Y; Pisani A; Martella G; Karouani M; Yamaguchi H; Pothos EN; Shen J. 2009. R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice. Proc Natl Acad Sci U S A 106(34):14622-7. [PubMed: 19667187] [MGI Ref ID J:151944]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred together.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
|
|
|
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Control Information
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 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.