2004 New Investigator Research Grant

Transgenic animal models of Alzheimer’s disease are animals that have been modified to carry human genes associated with Alzheimer’s and, as a result, develop Alzheimer-like brain disorders. These models are important for understanding the biology of the disease, clarifying links between brain changes and disease symptoms, and developing new drugs.

Most transgenic models in Alzheimer research are mice. These mice are usually created by injecting the desired human gene into a fertilized egg and then breeding populations of mice that have ended up with the desired genetic makeup. There are a number of factors that affect whether this process “works.” It is difficult to do with mice and has been generally unsuccessful with rats. A rat model may be preferred, however, because rat behavior is better understood, autopsies are easier to perform on rats than on mice, and each animal has a larger amount of tissue for analysis.

Michael P. Murphy, M.A., Ph.D., and colleagues are developing a rat model of Alzheimer’s disease using nuclear transfer, or cloning, technology. With this method, a donor cell’s nucleus (which carries all of an organism’s genetic information) is inserted into an egg that has had its own nucleus removed.

The researchers believe that advantages of this approach include (1) the ability to tweak the genetic profile of the donor cell into an “ideal model” before the transfer of the nucleus to an egg and (2) the potential likelihood of creating exact copies of this ideal model. This research may contribute to better models of Alzheimer’s disease and help determine the utility of this technology in animal model research.