Modification: LRRK2: Transgenic
Disease Relevance: Parkinson's Disease
Strain Name: FVB/N-Tg(LRRK2)1Cjli/J
Genetic Background: BAC injected into fertilized FVB zygotes. Founder mice bred with FVB/N inbred mice for many generations, and then with FVB/NJ inbred mice.
Availability: Available through The Jackson Laboratory, Stock# 009610, Live.
These transgenic mice overexpress human wild-type LRRK2 (Li et al., 2009). The mice develop normally and do not exhibit any known motor deficits.
The WT-OX model uses a bacterial artificial chromosome (BAC) to overexpress human LRRK2. The BAC encodes the entire gene with 29 kb upstream and 42 kb downstream. Expression is controlled by endogenous regulatory elements. Transgene expression was approximately five-to 10-fold above the level of endogenous mouse Lrrk2.
These mice have not been extensively characterized, but hemizygous appear similar to nonTg mice. They developed normally and did not exhibit overt motor deficits. The only reported behavioral test, the number of rearings in the cylinder test at 10 months of age, did not reveal significant differences from wild-type mice.
A 188 kb human bacterial artificial chromosome (BAC) containing the entire human LRRK2 gene, with 29 kb upstream and 42 kb downstream.
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
- Motor Impairment
- Dopamine Deficiency
- α-synuclein Inclusions
- Mitochondrial Abnormalities
- Cognitive Dysfunction
- Neuronal Loss
- Li Y, Liu W, Oo TF, Wang L, Tang Y, Jackson-Lewis V, Zhou C, Geghman K, Bogdanov M, Przedborski S, Beal MF, Burke RE, Li C. Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease. Nat Neurosci. 2009 Jul;12(7):826-8. PubMed.