CINCINNATI—Just like its namesake, the Marvin Mouse has a game plan—and if all goes well, it could lead to victory over a debilitating disease.
The Marvin Mouse is what researchers at the University of Cincinnati (UC) call a transgenic mouse that is being used as an animal model in experiments designed to shed light on how killer T cells contribute to multiple sclerosis (MS).
Some of the funding for their research has come from the Marvin Lewis Community Fund—a charitable foundation formed in 2003 by the Cincinnati Bengals head coach and his wife, Peggy—and is used to generate the Marvin Mouse. Having the mouse in place as a reagent helps bolster the research team’s case for grants from the National Institutes of Health (NIH).
“It’s important to be able to conduct detailed investigation of human disease mechanisms in animal models,” says Aaron Johnson, PhD, research assistant professor in the neurology department at UC’s College of Medicine and a former honorable mention all-state football player in Minnesota. “By gaining insight into what happens in human MS, you have the potential to design therapeutic targets to fight the disease.”
Says Lewis, a member of the UC Neuroscience Institute’s Advisory Board: “I am grateful that our donation is helping UC researchers learn more about multiple sclerosis through the Marvin Mouse. “This builds on the Angelo Papastamos Grant we funded, which was named after my brother-in-law who has MS.”
According to the National Multiple Sclerosis Society, MS is a chronic, often disabling disease that attacks the central nervous system—the brain, spinal cord and optic nerves. Symptoms range from numbness in the limbs to paralysis or loss of vision. Progress, severity and specific symptoms are unpredictable and vary from one person to another.
In MS, the body’s own defense system attacks myelin, the fatty substance that surrounds and protects healthy neurons (nerve fibers) in the central nervous system. When demyelination occurs, the neurons themselves can be damaged, disrupting nerve impulses traveling to and from the spinal cord and producing the variety of symptoms that can occur.
Johnson’s research focuses on killer T cells, which have drawn increasing scrutiny in the past 10 years (previous MS research predominantly focused on helper T cells). Numerous clinical studies have found killer T cells in close proximity to areas of demyelination where neurons and axons (the long fibers that conduct impulses away from the body of the nerve cell) were being severed.
“It doesn’t mean they did it,” Johnson says of the killer T cells, “but it’s kind of like the criminal at the scene of the crime. You need to develop animal models now to try and determine the mechanism by which this can occur.”
Johnson, with research technician Yi Chen, has done several studies to determine how killer T cells can contribute to disability in mouse models. Already, they have found that removal of killer T cells preserves motor ability and that killer T cells are able to disrupt the blood-brain barrier that keeps toxins in the blood from reaching the brain.
“To really get at how a T cell does this, you use the animal models,” says Johnson. “We need to find out what cell type in the central nervous system this T cell is specifically engaging. And in human MS, you will never get the answer to that question because you simply cannot do a mechanistic study in human beings.”
Using the Marvin Mouse, Johnson’s team has been able to develop a strategy by which it can silence the target of the killer T cells: the MHC class I molecule that they recognize on the surface of certain cell types. If the target is silenced, the killer T cells are effectively neutralized.
“In other words,” says Johnson, “the Marvin Mouse completely disrupts the ability for class I molecules to surface and can help define important interactions in neurological disease.”
The goal, Johnson says, is to continue to gain insight into what happens in human MS and gather information that will be helpful in designing therapeutic targets to protect cells in the central nervous system.