The overlap between the mouse genotype and the human genotype is shockingly large. Humbling as it may be, 99% of the genes found in mice have homologs in humans. That is, specific genes that have been isolated in mice function in similar or related ways in you and I. Since the 1980s, researchers have been taking full advantage of this fact, using transgenic mice to study human disease. Researchers manipulate the genome of mice to induce specific diseases that are also present in humans.
One method of gene manipulation involves the study of “knockout” mice. Researchers inactivate, or knockout, a specific gene in the mouse and study how its behavior and appearance has been altered in comparison to a normal, wildtype mouse. UC Davis has recently stepped on board of an international project, known as the Knockout Mouse Project, which aims to compile a comprehensive database of mouse genes. “By individually knocking out genes, we will be able to assess the specific role that each one plays in the mouse’s behavior,” said Peter Takeuchi, lab manager of the Mouse Behavioral Assessment Laboratory (MBAL) at UC Davis.
UC Davis will work in collaboration with other 19 other research institutes across the globe in order to assess and record the roles of 8500 genes. A total of $47.2 million has been awarded to participating institutes and organizations in support of the project, demonstrating the immense impact it is bound to have on the research community. Having a readily accessible database of characterized genes will save researchers time and money in the future. Joanne Suarez, Senior Research Associate at MBAL, is looking forward to being involved with such a large-scale project. “Most of the projects we deal with are local experiments for investigators in the UC community. It is exciting to be involved with an international project that will result in a resource that researchers around the world can continue to reference in the future,” she said.
Each knockout mouse will be tested in various ways to determine if and how the animal’s behavior is impaired. “We will be testing for any abnormalities in motor skills, pain threshold, gait and appearance,” explained Joanne. MBAL will also be recording metabolic behavior in the mice. The fancy looking equipment seen in the picture on the left is a monitoring system that can be used to track overall metabolic output. It factors in food and water intake, general activity and sleep cycles of the mice.
The final result of the project, which is expected to be a 5-year commitment for UC Davis, will aid researchers in gaining strategies on how to diagnose, treat and prevent many diseases. Mouse models are commonly used for studying human obesity, cancer, cardiovascular disease, diabetes, Alzheimer’s, arthritis and more. “The project is just in its beginning stages,” stated Dr. Mari Golub, MBAL director, “so it is hard to predict what may come of it.” She stressed that the impact of the project will rely on the cooperation of all of the participating organizations. She also added that MBAL is prepared to put in the time and effort that the project will require. “The research community has seen that UC Davis can handle these kind of difficult projects,” she concluded, “which is why they’ve put us on it.”