University of Virginia Health System

RESEARCHERS DEVELOP BETTER MODEL TO STUDY DISEASE

For the first time, scientists have engineered a gene in mice that can be turned on and off repeatedly without affecting the expression of non-targeted genes. This research involved genetic manipulation that caused mice to change color when a special supplement was added to their drinking water. The mice reverted back to their original color after the supplement was removed.

A research team from the University of Virginia Health System developed a new transgenic mouse model system that will enable scientists to make a more sophisticated model of human diseases. Heidi Scrable, assistant professor of neuroscience, led the research that was published in June 15th issue of Genes & Development.

The point of this research was to add another dimension to the control that we currently have in building mouse models of human diseases, Scrable said. In this case, the scientist can control when a gene will be expressed.

Scrable, along with U.Va. research assistants Carolyn Cronin and Wendy Gluba, borrowed a system from bacteria and transferred it into the mouse in such a way that it functioned the same way in the mouse that it did in the bacteria. According to Scrable, bacteria have evolved a simple system that allows them to turn genes on and off -- when the gene is needed, it is turned on and when the gene is not needed, it is turned off. This was accomplished by genetically engineering the bacterial lac operon for use as an inducible gene regulatory system in the mouse. The lac regulatory system provided reversible control of specific gene.

What we've been able to do is to take pieces of DNA from the genome of bacteria and transfer it into the mouse and get it to function the same way in the mouse, Scrable said. This is important to be able to gain experimental control over the timing of gene expression. It is currently possible to control 'where' a gene is expressed in the mouse, but hasn't been very reliable to control 'when' a gene is expressed. This system allows us to control 'when' a gene is expressed.

According to Scrable, this finding has widespread application. Currently, scientists try and re-create disease in the mouse to reveal the nature of mutations. With more sophisticated models, the researchers can better study how diseases arise from mutations in genes.

This technology will allow us to move beyond models of one gene, one disease category and get into modeling diseases that are more complicated such as heart disease, Alzheimer's disease or diabetes-diseases in which the one gene, one disease paradigm does not fit.

June 22, 2001