These knock-out mice lack exons 39-40 of the leucine-rich repeat kinase 2 (Lrrk2) gene and may be useful for studying the role of Lrrk2 in the progression of Parkinson's Disease.
Kuldip Dave, The Michael J. Fox Foundation
These mice lack exons 39-40 of the leucine-rich repeat kinase 2 (Lrrk2) gene, abolishing gene function. LRRK2 protein, also known as Dardarin, contains multiple functional domains and may function as both an active GTPase and kinase. LRRK2 may regulate alpha-synuclein-mediated neuropathology through modulation of intracellular trafficking and accumulation of SNCA protein. These mice may be useful for studying the role of Lrrk2 in the progression of Parkinson's Disease.
A targeting vector was designed to replace exons 39-40 of the leucine-rich repeat kinase 2 (Lrrk2) gene with a loxP-flanked neomycin resistance (neo) cassette. The construct was electroporated into C57BL/6NTac-derived B6-3 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a Cre recombinase expression plasmid to delete the neo cassette. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to C57BL/6NTac mice. Upon arrival, mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) for at least one generation to establish the colony.
In 2018, The Jackson Laboratory Repository began using an expanded 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains. This was performed on our rederived living colony. While the 43 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest our live colony is a C57BL/6N;C57BL/6J mix. Of note, the mice sent to The Jackson Laboratory Repository in 2011 (and used to freeze sperm) were on a C57BL/6N genetic background.
|Allele Name||targeted mutation 1.1, The Michael J Fox Foundation|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Lrrk2, leucine-rich repeat kinase 2|
|Strain of Origin||C57BL/6NTac|
|Molecular Note||A targeting vector was designed to replace exons 39-40 of the leucine-rich repeat kinase 2 (Lrrk2) gene with a loxP-flanked neomycin resistance (neo) cassette. Correctly targeted ES cells were transiently transfected with a Cre recombinase expression plasmid to delete the neo cassette. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to C57BL/6NTac mice.|
|Mutations Made By|| |
Yingbin Ouyang, Taconic
When maintaining a live colony, heterozygous mice may be bred to wild type mice from the colony or to C57BL/6NJ inbred mice (Stock No. 005304).
When using the Lrrk2 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #016121 in your Materials and Methods section.
"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.