Model 13940 is a constitutive Knock-In (KI) of the mouse LRRK2 gene. The human G2019S point mutation has been introduced into exon 41 of the mouse LRRK2 gene.
- The G2019S alpha-mutation is linked to the development of Parkinson's disease, both sporadic and familial1.
- In patients, the G2019S LRRK2 mutation is an autosomal dominant mutation that leads to pathology similar to what is observed with idiopathic Parkinson's disease.
- At 18 months of age, LRRK2 G2019S mice show an increased locomotor response after amphetamine challenge.
- This knock-in mutation does not appear to affect basal motor function or more complex behavior in C57BL6 mice.
- The allele has 2 loxP sites at either side of exon 41, thus this line can be crossed to a cre line of choice in order to excise the mutation-carrying exon 41. However, successful excision has not been verified and, even if successfully excised, it is not certain that would lead to loss of Lrrk2 function as exon 41 (out of 51 total exons) is late in the gene, and a partial protein may be produced after cre/lox recombination.
Orders by weight: Taconic cannot accept orders by weight for this model. Please note that shipments may contain animals with a larger weight variation.
Ordering Note for Controls: Model 13940 WT littermate controls are not available for this model due to the homozygous mating format. A recommended WT control option is to utilize
C57BL/6NTac commercial animals sourced from our Cambridge City, Indiana production site (the same location where model 13940 is bred). Model 13940 has been generated and maintained on the C57BL/6NTac genetic background.
What our customers say:
“Robust, well-validated pre-clinical models of Parkinson's disease are a necessary tool for understanding the biology and possible treatment of this complex disease. With dedicated project management and technical support, Taconic has been a reliable partner in The Michael J. Fox Foundation's efforts to provide the research community with important, field-enabling pre-clinical models. We look forward to continuing to partner with Taconic for custom model generation projects.”The Michael J. Fox Foundation
Genetic Background:
C57BL/6NTac Background Origin:
To generate the constitutive KI Lrrk2tm4.1Arte mice, targeting vectors having proximal loxP and frt-flanked PGK–neomycin cassettes were inserted into intron 41; a distal loxP site was inserted into intron 42 of the endogenous mouse LRRK2 gene. The vectors were introduced into C57BL/6NTac-derived ES cells. Successfully targeted ES cells were injected into blastocysts, and then chimeric mice were bred with a Flp deleter strain to remove the selection neo cassette. Mice were then bred with C57BL/6NTac mice to remove the Flp transgene. The colony is maintained by mating a homozygous males and females. Taconic received stock from Artemis in 2007 and introduced it into barrier production after the mice went through embryo transfer derivation. Source:
Model Sponsor: The Michael J. Fox Foundation Availability:
As of April 1, 2018, The Michael J. Fox Foundation for Parkinson's Research (MJFF) has instituted a new ordering policy for this model in an effort to prevent delays in order fulfillment, ensure models are shipped at the desired age, and maintain affordable pricing for all researchers accessing MJFF models. To achieve these goals, the new MJFF policy dictates that no one group can deplete the MJFF-sponsored colony. As such, orders will be limited to a total quantity of approximately 15-20 per researcher per month. Average lead time and age range may vary based on quantity and sex requested. Researchers requiring orders above this amount should establish a dedicated colony for their own use, either by breeding in-house or contracting with Taconic. For questions or concerns, please email
tools@michaeljfox.org.
Color:
Black Species:
Mouse Initial Publication:
Matikainen-Ankney BA, et al. 2016. Altered Development of Synapse Structure and Function in Striatum Caused by Parkinson's Disease-Linked LRRK2–G2019S Mutation. J Neurosci. Jul 6; 36(27): 7128–7141. PMID: 27383589.
