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JCI table of contents: Nov. 8, 2007
Date:11/8/2007

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View the PDF of this article at: https://www.the-jci.org/article.php?id=32249


TECHNICAL ADVANCE: New mouse strain teaches us about GPCRs

All mammals, including humans, have hundreds of proteins known as GPCRs. The function of some of these GPCRs is known and in many cases has been shown to regulate disease processes. However, the function of very many GPCRs remains incompletely understood. A new tool to determine the in vivo function of GPCRs in mice has now been generated by Shaun Coughlin and colleagues from the University of California at San Francisco.

The authors generated mice (ROSA26PTX mice) that have the capacity to express a toxin known as PTX, which inhibits signaling by proteins that transmit signals from GPCRs (Gi and Go G proteins), in any tissue. However, expression of PTX only occurs in the presence of another protein known as Cre. The role of GPCRs in beta-cells in the pancreas was determined by mating ROSA26PTX mice with mice expressing Cre only in pancreatic beta cells. These mice had high levels of the hormone insulin in their blood and were resistant to diet-induced obesity. Further analysis determined new roles for the GPCRs alpha-2A-adrenergic receptor, Taar1, and Par2 in regulating insulin release by pancreatic beta cells. By mating ROSA26PTX mice with other strains of mice expressing Cre in a tissue or cell-type restricted manner it will be possible to determine the function of GPCRs in these specific tissues and cell types.

TITLE: Probing cell typespecific functions of Gi in vivo identifies GPCR regulators of insulin secretion

AUTHOR CONTACT:
Shaun R. Coughlin
UCSF School of Medicine, San Francisco, California, USA.
Phone: (415) 476-6174; Fax: (415) 476-8173; E-mail: Shaun.Coughlin@ucsf.edu.

View the PDF of this article at:

Contact: Karen Honey
press_releases@the-jci.org
215-573-1850
Journal of Clinical Investigation
Source:Eurekalert

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