LRRK2 is the most recent gene linked to PD and mutations in the gene represent one of the most common genetic causes of PD identified to date. However, little is known about the function of the LRRK2 protein product for this gene or how alteration of its function relates to PD pathogenesis. Mutations in LRRK2 gene are responsible for Park8 type of familial Parkinson's disease. To better understand the pathogenesis, we are establishing pre-clinical models using our Bacterial Artificial Chromosome (BAC)-mediated transgenic technology. This technology allows accurate expression control of the transgene, and likely will help us make pre-clinical models that recapitulate cardinal PD pathology. These pre-clinical models, once established, will be powerful tools for disease mechanistic study, and for testing potential drug candidates.
Final Outcome
Dr. Li successfully generated LRRK2 BAC transgenic mice expressing mutant LRRK2 and has been characterizing these mice for phenotype. These mice show levodopa-responsive behavioral abnormalities as well as evidence of axonal degeneration. Further characterization is ongoing and the mice are being transferred to Jackson Laboratories for practical accessibility to other researchers in the field.
Dr. Li also has been awarded supplemental funding to examine the LRRK2 mice for possible dysfunction of the mitochondria in order to better understand the normal and pathogenic function of LRRK2.
Results of this work were published in Nature Neuroscience.
Researchers
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Chenjian Li, PhD