Research Models

LRRK2 WT Mouse (BAC Tg)

Synonyms: WT-OX, LRRK2 WT BAC, WT LRRK2 Mouse (BAC Tg), WT LRRK2 BAC Tg Mouse (Li)

Species: Mouse
Genes: LRRK2
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.

Modification Details

A 188 kb human bacterial artificial chromosome (BAC) containing the entire human LRRK2 gene, with 29 kb upstream and 42 kb downstream.

Phenotype Characterization

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

No Data

  • Neuronal Loss
  • Dopamine Deficiency
  • α-synuclein Inclusions
  • Neuroinflammation
  • Mitochondrial Abnormalities
  • Cognitive Dysfunction

Dopamine Deficiency

No data.

α-synuclein Inclusions

No data.

Neuronal Loss

No data.


No data.

Motor Impairment

Not observed.

Mitochondrial Abnormalities

No data.

Cognitive Dysfunction

No data.


  1. LRRK2 R1441C Mice Recapitulate PD Motor Deficits
    The recent article by C.J. Li’s group reports on the first transgenic LRRK2 mouse model. The LRRK2 mouse uses a BAC system to express WT or R1441C LRRK2, which is a mutation in the GTPase domain of LRRK2. The benefit of the BAC system is that it permits use of the LRRK2 promoter, which allows for an expression pattern that is elevated but exhibits a distribution that recapitulates the pattern of endogenous LRRK2. The mouse is notable in several respects. The most important observation is that the mouse exhibits age-dependent motor deficits that are responsive to L-DOPA, which is a classic phenotype observed in patients with Parkinson disease and shows that the motor deficits derive from dysfunction of dopaminergic neurons. The nature of the dysfunction, though, is not entirely clear. The group reports a modest decrease in dopamine release from the neurons. This phenotype is reminiscent of phenotypes observed for parkin and PINK1 mice, and might be a preliminary indication that deficits in dopamine release are a common feature of genes associated with PD. A second encouraging observation is that mice show signs that are commonly associated with neuronal degeneration. The researchers observe tyrosine hydroxylase positive spheroids, and increased tau phosphorylation, shown with the AT8 antibody.

    These degenerative phenotypes are interesting for what they do and do not show. On the positive side, the morphologic changes are consistent with a hypothesis that there is degeneration of dopaminergic neurons. Spheroids are a common, non-specific sign of neurodegeneration. Tau phosphorylation is also an early sign of neuronal degeneration, or at least neuronal stress. From my perspective, the evidence of dopaminergic degeneration is quite believable because it is consistent with what we observe in our C. elegans model, which has been in review for over a year and hopefully will be out soon. The presence of phospho-tau reactivity is also interesting because neurofibrillary tangles are observed in some cases of LRRK2-associated parkinsonism, and because polymorphisms in tau are strongly associated with Parkinson disease, being the second strongest result observed in multiple GWAS studies after those in α-synuclein. On the negative side, the manuscript is striking for the absence of any mention of loss of dopamine neurons or the presence of α-synuclein inclusions or Lewy body pathology. This might mean that expressing mutant LRRK2 alone is insufficient to recapitulate Parkinson disease and one needs to also have the human proteins present, such as α-synuclein and tau. Alternatively, this might reflect the vagaries of transgenic models, and some other models might show α-synuclein pathology (although I am not aware of any reports of α-synuclein pathology in the other mouse models that are in development). Nevertheless, the presence of a L-DOPA responsive transgenic mouse model derived from a genetic mutation associated with Parkinson disease represents an important advance for the field.

    View all comments by Benjamin Wolozin

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Paper Citations

  1. . Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson's disease. Nat Neurosci. 2009 Jul;12(7):826-8. PubMed.

External Citations

  1. The Jackson Laboratory, Stock# 009610

Further Reading