Flagmor transgenic mouse
OHSU # 1402
- John Williams, VI.Vollum Institute
FLAGMOR transgenic mice provides an advantage to studying signal transduction of mu-opioid receptors (MOR) through the activation of potassium-ion channels, desensitization, and receptor trafficking. A better understanding of the underlying mechanisms of MOR activation will lead to improved opioid treatment and research.
Mu-opioid receptors are a class of G-protein coupled receptors found primarily in the CNS and the GI system. The activation of MOR by opioids cause decreased perception of pain, decreased reaction to pain, and increased pain tolerance by inhibiting excitatory pathways.
The mice in this invention express an epitope-tagged mu-opioid receptor (FLAGMOR) targeted to catecholamine neurons. The FLAGMOR transgene was generated by manipulating and regulating molecular elements of the tyrosine hydroxylase gene. These mice are used to analyze the process of opioid receptor signaling.
Opioids are one of the oldest classes of analgesics. The opioids market is expected to grow from $9.6 billion in 2008 to $11.9 billion in 2018. There continues to be significant unmet needs for treatment of pain. Therefore, research and development of opioid treatment remains dynamic.
No other such mice are known to exist.
After earning his Ph.D. in Pharmacology from Loyola University in 1979, John Williams worked as a research scientist at the Max-Planck Institute in Munich and at Loyola University School of Medicine. He then spent five years as a research scientist in Biological Sciences at the Massachusetts Institute of Technology. In 1987, he became an assistant staff scientist at the Vollum Institute and rose to the position of senior scientist in 1996. He holds a concurrent appointment in the Department of Physiology and Pharmacology in the School of Medicine. Williams earned his B.S. from St. Lawrence University and his M.S. from the State University of New York at Potsdam.
Dr. Williams continues to utilize these mice to investigate events of opioid receptor signaling and G-protein coupled receptor trafficking that can potentially lead to the development of treatment for opioid tolerance in patients.
Arttamangkul, S., Quillinan, N., Low, M.J., von Zastrow, M., Pintar, J., and Williams, J.T. (2008) Differential activation and trafficking of mu-opioid receptors in brain slices. Mol. Pharmacol. 74:972-979.
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