Mouse Genomics Offers Insight on Human Counterparts

	Transgenic mice at the Seattle Comparative Mouse Genome Center.

Dr. Warren Ladiges and Dr. Carol Ware understand supply and demand.

Ladiges and Ware help develop transgenic mice at the Seattle Comparative Mouse Genome Center (SCMGC), one of five centers in the Comparative Mouse Genome Consortium funded by the National Institute of Environmental Health Sciences.

“We’ve definitely seen the demand for transgenic mice increase,” said Ladiges, professor of comparative medicine and director of the SCMGC.

Ware, assistant research professor of comparative medicine adds, “We cross a number of disciplines because researchers from many fields can come to us to have their mouse models generated. The process is challenging and technically difficult, so individual laboratories could not be expected to be expert in this area.”

Mice are increasingly important in basic and clinical research, because mice share all but one percent of their genes with humans. Mice are also relatively inexpensive to maintain and have a rapid reproductive cycle. Once a new human gene variant is found, researchers can compare the human version with its mouse counterpart.

“What we’re trying to do is identify variations that are relevant to specific diseases and generate humanized mouse models to see if, in fact, the variant could be used in studying risk factors associated with a disease or in managing those factors,” said Ladiges.

Humanized mouse models, mice injected with human genes containing specific variations, offer insight into how a genetic variation influences the development of and physiological response to diseases.

“Some variations in the DNA are very subtle,” said Ware. “It takes some kind of environmental trigger or challenge to determine if a variation has any effect on the overall health of the animal.”

Seattle Comparative Mouse Genome Center researchers are particularly interested in genetic susceptibility to environmentally induced diseases, such as heart disease, breast cancer, and colon cancer. A number of mouse models are also being used to investigate aging and age-associated diseases such as Werner’s syndrome, Alzheimer’s disease, and other neurodegenerative conditions.

“In a four-year period,” said Ladiges, “in collaboration with the Nathan Shock Center for Excellence in the Biology of Aging, we generated 30 mouse lines representing more than 30 mutations relevant to studying aging processes.”

The other centers in the national consortium are at the University of Cincinnati, Harvard University, the University of Texas Health Science Center at San Antonio, and the University of Texas M.D. Anderson Cancer Center. Each of the centers has specific areas of expertise.

Other than the transgenic facility, the Seattle Comparative Mouse Genome Center’s strengths include associations with longstanding UW research programs such as the positron emission tomography program in the Department of Radiology and the cell imaging facility in the Department of Pathology. Recent programs include the UW’s new Microarray Center and the gene variant discovery program in the Department of Genome Sciences.

“We expect to continue to work with a variety of different departments on campus and at the Fred Hutchinson Cancer Research Center,” said Ladiges. “Transgenic mouse research will provide novel insights for a variety of different fields. This is exciting new territory.”