When the bile ducts of mice were tied off, preventing bile from reaching the intestine, adding GW4064 prevented damage to the intestines, showing that it can replace bile in protecting the small intestine.
Genetically engineered mice that lacked FXR showed overall damage to the intestines, "strong evidence that this protein is crucial," Dr. Kliewer said. Drugs that bind to FXR, he said, could eventually become useful in treating various conditions of the small intestine.
Other UT Southwestern researchers involved in the study were Drs. Takeshi Inagaki and Guixiang Zhao, postdoctoral research fellows in molecular biology; Dr. Antonio Moschetta, postdoctoral research fellow in pharmacology and a research associate in the Howard Hughes Medical Institute; Youn-Kyoung Lee, student research assistant in molecular biology; Li Peng, senior research associate in molecular biology; John Shelton, senior research scientist in internal medicine; Dr. James Richardson, professor of pathology; Dr. Joyce Repa, assistant professor of physiology; and Dr. David Mangelsdorf, professor of pharmacology and biochemistry and an HHMI investigator. Drs. Ruth Yu and Michael Downes of the Salk Institute for Biological Studies in La Jolla, Calif., also participated in the study.