Mimicking a human disease in mice: a new model for the Parkinson related illness multiple system atrophy

In this month`s issue of EMBO Reports Kahle et al. describe how they genetically engineered a mouse to show pathological symptoms similar to those of human patients suffering from the neural disease Multiple System Atrophy (MSA), also known as Shy-Drager-Syndrome. The model could help researchers to develop and test new efficient drugs against this wide spread disease.

More than 100,000 Europeans and 100,000 US-Americans suffer from MSA. Affected individuals either show symptoms similar to those of patients suffering from Parkinson`s Disease or have a strong deterioration in their sense of balance. For this reason the disease is often diagnosed incorrectly. Doctors know very little about the pathology of the disease. However, one characteristic is that some brain cells show abnormal changes. Affected mature oligodendrocytes, the cells that form the isolating outer layer surrounding nerve fibers, produce a small protein called alpha-synuclein. They deposit this protein in the form of pathological structures called glial cytoplasmic inclusions.

Healthy mature oligodendrocytes do not produce this protein at all.
Kahle and colleagues “implanted” the human gene for the alpha-synuclein
protein into the mouse genome. As a result, the researchers found insoluble inclusion bodies of alpha-synuclein in the mouse`s oligodendrocytes. “In patients, the affected cells die as the individual ages. This is something we could not yet observe in our mice,” says Philipp Kahle, a researcher at the Ludwig Maximilian University, Munich, Germany. “But we are confident that in a next step we can produce mice that will also show this symptom. This will help us to understand more about the disease and can help researchers to develop and test drugs against multiple system atrophy.”

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