The Michael J. Fox Foundation for Parkinson’s Research didn’t waste any time putting recently published knockout rat technology to work.1,2 The foundation and Sigma-Aldrich Corp. have partnered to develop models of Parkinson’s disease and hope to make five rat models available for research use within a year.
In July, Sigma-Aldrich, in collaboration with Sangamo BioSci- ences Inc., Open Monoclonal Technology Inc. and the Medical College of Wisconsin, published the first targeted rat gene knockout, in Science. The knockout was produced using zinc finger nuclease (ZFN) technology developed by Sangamo. ZFNs induce targeted, double-stranded DNA breaks that can snip out specific genes of interest in a genome.3
The foundation and Sigma-Aldrich think PD is an ideal application for the technology because the disease lacks models and because rats provide a good representation of the human neurological system.
There is no mouse model of PD that accurately recapitulates the human condition.
“Two aspects go into finding the right models: the ability to mea- sure neurological defects and the ability to show symptomatically what is seen in Parkinson’s disease,” said Kirsten Carlson, associate director of research programs at the Michael J. Fox Foundation.
“While we know that it isn’t possible to exactly replicate the human disease, we want to develop a behavioral manifestation of what is seen in the disease,” she told SciBX. “Good symptomatic models and good models that show what’s going on in the brain do exist, but the Holy Grail of animal models of Parkinson’s disease is to develop one that captures both.”
Philip Simmons, global marketing and business development man- ager at Sigma Advanced Genetic Engineering (SAGE) Labs, said the fact that rats are smarter than mice and have both behavioral and cognitive characteristics that are similar to humans is important for replicating the features of PD and for measuring the efficacy of treatments.
“It was natural to consider neurobiological and neurodegenerative conditions for the knockout rats based on the superior brain func- tions of these animals,” he told SciBX. “It could be more predictive for Parkinson’s disease or Alzheimer’s disease than mouse models allow.”
Carlson agreed. “We might be able to develop the rat into a more suitable model,” she said. “Rats are also larger organisms, which allows researchers to harvest more tissue from them in preclinical research and can allow for imaging studies that might be more dif- ficult in smaller animals.”