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JCI online early table of contents: Dec. 1, 2010
Date:12/1/2010

articles/view/39828?key=0bb497688c5428a246bd


HEPATOLOGY: The proteins FXR and SHP work together to regulate bile acid levels

Bile acids, which are made in the liver, are involved in numerous biological processes, including digestion of fats, liver regeneration, and energy expenditure. Levels of bile acid are tightly regulated by a feedback loop. Current models place the protein FXR upstream of SHP in a linear pathway within this feedback loop. Now, a team of researchers, led by David Moore, at Baylor College of Medicine, Houston, has shown that in mice FXR and SHP act in parallel within the feedback loop that regulates bile acid levels. Of particular interest was the observation that mice lacking both FXR and SHP showed substantially more severe defects in regulation of bile acid levels than did mice lacking either of the proteins alone. Furthermore, as mice lacking both FXR and SHP developed cholestasis (the accumulation of bile acids in the liver) and liver injury at just 3 weeks of age, the authors suggest that these animals could provide a model for juvenile onset cholestasis, a term that encompasses several genetic diseases including progressive familial intrahepatic cholestasis.

TITLE: Combined deletion of Fxr and Shp in mice induces Cyp17a1 and results in juvenile onset cholestasis

AUTHOR CONTACT:
David D. Moore
Baylor College of Medicine, Houston, Texas, USA.
Phone: 713.798.3313; Fax: 713.798.3017; E-mail: moore@bcm.edu.

View this article at: http://www.jci.org/articles/view/42846?key=061626916eb46a68a308


HEPATOLOGY: Uncovering the in vivo function of the protein Fbxw7 in the liver

Uncovering the in vivo function of the protein Fbxw7 has been difficult because mice lacking Fbxw7 die in utero. However, by selectively deleting Fbxw7 in
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