Reporter gene has much to tell research scientists

By Kristen Holland Shear / October-November 2010

In a study available in PLoS One, the Public Library of Science’s online journal, UT Southwestern researchers describe a new noninvasive method to track whether genes introduced into research animals are functioning properly.

Dr. Ralph Mason, professor of radiology and senior author of the paper, said the work has potential applications in characterizing tumors and monitoring the effectiveness of cancer treatments, as well as for evaluating stem-cell transplants. The work also might be applicable to gene therapy, where physicians struggle to determine whether a normal functioning gene “takes” when injected into a patient with a genetic disease.

Dr. Ralph Mason

Scientists often introduce specific so-called reporter genes into the tissues of research animals in order to investigate the function and activity levels of those genes. Researchers can track a reporter gene’s product, which then provides information such as whether the gene of interest hit its target and if it is being expressed.

The most popular reporter gene historically has been lacZ, which generates the enzyme beta-galactosidase and has been the foundation for routine assay of genetic manipulation for 50 years. It has been used in preclinical studies as well as in patients.

Tracking the reporter gene, however, often requires inserting a needle into the research animal’s tissue, potentially damaging the tissue. Noninvasive imaging methods are preferable, Dr. Mason said, and bioluminescent imaging based on luciferase, the chemical that allows fireflies to flash, has become popular for monitoring biological processes in small live animals.

In the new study, Dr. Mason and his colleagues report the ability to evaluate beta-galactosidase based on light emission using a chemiluminescent approach. The researchers watched tumors “glow” using standard optical imaging technology to detect how the enzyme – and its gene cargo – functioned within an animal.

“We are hopeful that we’ll be able to use this technology to observe deeper tumors noninvasively, avoiding potential tissue damage caused by direct needle insertion into the tissue,” Dr. Mason said.

An obvious benefit to this work, Dr. Mason said, is that researchers can use existing technology to track the delivery and function of inserted genes in live animals.

 “We can use commercial optical imaging instruments, which are much less expensive than radionuclide or magnetic resonance devices,” he said.

The new approach also greatly enhances the flexibility of small-animal imaging research. “Chemiluminescence offers a whole new paradigm for efficient small-animal research,” Dr. Mason said.

Dr. Li Liu, instructor of radiology at UT Southwestern, was lead author of the study.