Knockout mice program established at UA

Gene targeting revolutionized the way scientists use mice to study the function of genes. Also called “knockout” technology, the technique allows scientists to create animal models of human disease. After the decoding of the mouse and human genomes in the early part of this decade unearthed thousands of new genes of unknown function, knockout mice became a prime source of information for making sense of them. Most human genes can be studied by looking at mouse genes because the protein-encoding genes of both are 85 percent identical in sequence.

Scientists have developed hundreds of mouse models of human ailments, including heart disease, diabetes, degenerative brain disorders and cancer. The three scientists who developed this technique won the Nobel Prize in Medicine this year. BIO5 member Tom Doetschman, PhD, a professor in the College of Medicine at The University of Arizona (UA), played an active role in the mid 1980s in the lab of one of those winners, Oliver Smithies, PhD, of the University of North Carolina Chapel Hill. While in Dr. Smithies' laboratory, Dr. Doetschman published two papers that played a significant role in the award.

(See http://nobelprize.org/nobel_prizes/medicine/laureates/2007/adv.html for further details on the award.)

Dr. Doetschman arrived at the UA in early 2006 from the University of Cinncinati, bringing with him his research program and a reknowned genetically engineering mouse model program. Two years ago, the National Institutes of Health (NIH) began funding the “knockout” of every gene in the mouse genome – all 30,000 of them. Dr. Doetschman’s lab in Cinncinati was responsible for knocking out 300 of them before he relocated to Arizona where he is continuing with that work as a service to all University researchers.

“Since the time of Mendel, we have studied what goes wrong when a gene is mutated. The beauty of the mouse as an experimental organism is that we can mutate a specific gene in a pre-planned way and then learn the consequences of that alteration at the whole animal level in a mammal with considerable genetic similarity. As a result, we can understand the function of the gene and why specific genetic mutations can cause human disease,” says Dr. Doetschman, who has a doctorate in biochemistry and biophysics from the University of Connecticut and completed three postdoctoral fellowships before establishing his lab at the University of Cincinnati.