LRRK2 knockouts normal, not hypersensitive to MPTP

A new study published in the Journal of Neuroscience characterizes the phenotype of a LRRK2 knockout mouse. These mice are viable and show no major abnormalities, including a normal dopaminergic system. Additionally, these knockout mice did not show any difference in susceptibility to MPTP from the wild type controls.

LRRK2 mutations are the most common mutations associated with Parkinson's disease. This study elucidates further how the kinase activity of LRRK2 can contribute to neurodegeneration. Foremost, Drs. Ted and Valina Dawson demonstrate that loss of LRRK2 does not lead to neurodegeneration in the mouse, indicating little to no role in development or survival.  Secondly, LRRK2 loss of function does not exacerbate susceptibility to the neurotoxin MPTP (an inhibitor of mitochondrial complex I).

The function of LRRK2 remains unknown. However, common mutations to LRRK2 are theorized to lead to a gain-of-function. Though the knockout shows no defects, it does not preclude the possibility of increased LRRK2 kinase activity influencing dopaminergic architecture and/or susceptibility to neurotoxins such as MPTP.