On a test of attention—in which rats must touch one of five screens when a light appears—the SHANK3 rats do just as well as controls when the light stays on for a long time. But their performance slumps as the light flashes for shorter durations, says Hala Harony-Nicolas, a molecular neuroscientist at Mount Sinai, who reported the results in January. Unlike controls, the SHANK3 rats also do not remember rats they have met the day before. When these rats receive the hormone oxytocin—often touted as a treatment for autism—the animals recover their social-recognition memory and attention skills.
As with other studies that use models with a single-gene mutation, a larger goal is to gain insights that will also apply to autism arising from other causes. In the case of SHANK3, Harony-Nicolas says, mutations in other genes interfere with the same brain pathways, making oxytocin potentially useful beyond Phelan-McDermid. Some researchers are already studying oxytocin treatment in clinical trials of people with Phelan-McDermid syndrome.
There are still plenty of hurdles yet to overcome, including cost: Rats can be five times more expensive to care for than mice. Overall, though, rat research is on the upswing. There are at least two dozen rat models available, and more being made. Some of the newer ones will likely have point mutations, which alter one section of DNA instead of an entire gene.
Eventually, rat models could become as complex as their mouse counterparts, with mutations that can be manipulated to turn on or off during development. Scientists are also forging new collaborations, often across rodent and mutant lines. Kind’s group, for example, is working with researchers in Bangalore, India, to look for behavioral patterns among nine rat models of autism. He has also shipped his rats to numerous other labs in the United States and the United Kingdom.
In another project, the Preclinical Autism Consortium for Therapeutics, three U.S. labs are working together; two use mice, and the third is focused on rats. By combining data from both types of rodents in studies of behavior, electrical activity and molecular pathways in the brain, the team hopes to provide pharmaceutical companies with reliably vetted targets for drug development, says Mustafa Sahin, a developmental neurobiologist at Harvard University. “Single laboratory studies on a single mouse model were not providing sufficient confidence in the pharmaceutical industry to invest in autism spectrum disorder,” Sahin says.
Rats may never replace mice, nor should they. But together, both types of rodents can offer more to science than either could alone, Samaco says.
His team is betting on it: Last year, Baylor’s rat lab underwent a major renovation. The lab, expected to reopen by the end of March, will feature more than 1,000 square feet dedicated to following rats into adulthood. “There are so many papers we’re preparing right now on various rat models,” Samaco says. This year, he predicts, will be the year of the rat.
This article appears courtesy of Spectrum.