Investigation of Possible Pathological Changes in Aged LRRK2 Knockout Models
MJFF Research Grant, 2012
To determine if there are any pathological changes in either the brain, kidney, lung, spleen, liver, and heart in aged LRRK2 knockout and wild type pre-clinical models using both light and electron microscopy.
The various tissues outlined above will be fixed and processed for both light and electron microscopic analysis. Any abnormalities of the tissues listed above in the LRRK2 knockout models will be photographed and compared against the wild type models.
Relevance to Diagnosis/Treatment of Parkinsonís Disease:†††††††††††††††††††††
Since mutations of the LRRK2 gene have been determined to be a risk factor for the development of Parkinsonís disease, knockout models have been developed as a tool to be used in this research.† Determining if there are detrimental affects on various tissues of the body in these knockout models is the focus of this project.
We predict that based on a previous study using LRRK2 knockout models, there will be pathological changes in peripheral tissue (i.e., liver, kidney, lungs, heart, spleen), but no changes in the brain.
We utilized a pre-clinical model in which a specific gene, LRRK2, was eliminated after the models were born. We determined if there were any tissue changes in several organs including liver, kidney, and lung. We used both a light microscope and an electron microscope to investigate detailed alterations in these tissues.† Mutations of this gene have been implicated as a risk factor for Parkinsonís disease. We found that there were pathological changes in these 3 organs of the pre-clinical model.† This suggests that the lack of this gene starting at the time of development will result in tissue damage over a long time period.† A mutation of this LRRK2 gene results in increased function and there is a significant effort to develop drugs that will block or inhibit this gene. Therefore, if this gene is not functional for a long period of time, it is possible that select tissue damage could take place.† Our results suggest that careful monitoring of kidney, lung and liver function needs to be considered.
Research Biologist and Professor at VA Medical Center and Departments of Behavioral Neuroscience and Pathology, Oregon Health & Science
Location: Portland, Oregon, United States
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