New Mouse Model of Parkinson’s Disease Developed

Using a new technology for inserting large DNA sections into a genome, scientists have successfully created a mouse model of Parkinson’s disease that has the same impairments of movement and degenerative brain changes as the human disease, according to a study published online June 7 in Nature Neuroscience.

Yanping Li, from Weill Medical College of Cornell University in New York City, and colleagues used a transgenesis technology known as bacterial artificial chromosome to insert into the mouse genome a full length leucine-rich repeat kinase 2 (LRRK2) gene that carries hR1441G, a common missense mutation that causes Parkinson’s disease. Another cohort of littermate mice that did not receive the LRRK2 insertion served as a control group.

The researchers report that mice with the mutant gene developed all of the main features of Parkinson’s disease, including the slowness of movement associated with diminished dopamine release, a biochemical effect confirmed by intrastriatal microdialysis. At 10 to 12 months, the transgenic mice exhibited the immobility characteristic of Parkinson’s disease. Significantly, levodopa and apomorphine, used in the treatment of Parkinson’s disease in humans, both reversed the severe motor deficits in the transgenic mice.

“hR1441G LRRK2 bacterial artificial chromosome transgenic mice offer, for the first time, a model of Parkinson’s disease based on a known genetic cause that successfully recapitulates the motor behavioral, neurochemical and histopathological features of the human disease. Therefore, it will be a powerful tool for in vivo mechanistic studies and therapeutic development,” the authors conclude.

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