In the study, Dr. Yue developed two mouse models with the normal or mutant LRRK2 using an advanced form of genetic engineering called bacterial artificial chromosome genetics (BAC). BAC gives scientists more control over where and when a foreign gene is expressed in the target animal. Dr. Yue and his team genetically engineered a fragment of genomic DNA containing a human Parkinson's disease mutation of LRRK2 and injected it into the mice.

How LRRK2 functions is unknown, but Dr. Yue and his team showed that the mutant LRRK2 produces too much so-called kinase activity in the brain. They are now pursuing the question whether the increased kinase activity accounts for the reduced dopamine levels, subsequently leading to neurodegeneration.

"Not having a mouse model has been a significant barrier to bringing the LRRK2 breakthrough from bench to bedside," said Dr. Yue. "The new model likely replicates the earliest stage of Parkinson's disease, giving us the opportunity to understand the biochemical and molecular events that cause the disease."

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine