UCLA scientists have developed a fast new way to image how thousands of genes misfire proteins in a mouse model of Parkinson’s disease. The approach may provide a research blueprint for pinpointing the abnormal brain regions linked to autism and schizophrenia.
The new findings are reported in the June edition of Genome Research.
Last year, UCLA pharmacologist Desmond Smith developed a new method to rapidly track how genes express proteins in the human brain. Called “voxelation,” the approach involves cutting the brain into cubes, then using DNA chip technology and math to reconstruct gene expression patterns in three-dimensional images.
This time, Smith used voxelation to compare gene expression in the brains of mice. Half of the mice received drugs to induce Parkinson’s disease. The UCLA team analyzed the brain cubes with DNA chips to track the expression of 9,000 genes simultaneously. They then combined the 9,000 resulting images to visualize how the genes construct the brain.
When they compared the colored brain images of the healthy and diseased mice, Smith and his colleagues discovered that the brains of the mice with Parkinson’s disease showed an abnormal shift in gene activity. The patterns of gene expression had moved and were not located in the brain where they should have been.
“This approach identifies which genes play a role in abnormal brain function and where they are located,” said Smith, UCLA assistant professor of molecular and medical pharmacology. “We can use this information to narrow down the brain regions linked to genetic disorders and pinpoint the genes responsible for causing them.”
The UCLA study was funded by the National Institute of Drug Abuse, Staglin Music Festival, National Alliance for Research on Schizophrenia and Depression, National Science Foundation, National Foundation for Functional Brain Imaging, Dana Foundation, Merck Genome Research Institute and W.M. Keck Foundation.
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