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.
Darren J Moore, Van Andel Research Institute
Valina Dawson, The Johns Hopkins University
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.
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.
|Expressed Gene||LRRK2, leucine rich repeat kinase 2, human|
|Site of Expression|
|Allele Name||transgene insertion 340, Darren Moore|
|Allele Type||Transgenic (Inserted expressed sequence, Humanized sequence)|
|Allele Synonym(s)||Tg(PDGFB-LRRK2*G2019S)340Djmo; transgene insertion 340, Darren Moore|
|Gene Symbol and Name||Tg(PDGFB-LRRK2*G2019S)340Djmo, transgene insertion 340, Darren Moore|
|Promoter||PDGFB, platelet derived growth factor subunit B, human|
|Expressed Gene||LRRK2, leucine rich repeat kinase 2, human|
|Strain of Origin||(C57BL/6J x C3H/HeJ)F1|
|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.|
|Mutations Made By|| |
Darren Moore, Van Andel Research Institute
When maintaining a live colony, hemizygous mice may be bred to wildtype (noncarrier) mice from the colony.
When using the G2019S-LRRK2 mouse strain in a publication, please cite the originating article(s) and include JAX stock #016575 in your Materials and Methods section.
|Hemizyous or Non Carrir for Tg(PDGFB-LRRK2*G2019S)340Djmo|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.
"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"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "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 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, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
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, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
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, PRODUCTS or SERVICES 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.