JCI table of contents: Feb. 21, 2008

The production of oxygen radicals, such as superoxide, by immune cells known as phagocytes is crucial in the fight against infection with microorganisms. Phagocytes use a protein complex known as phagocyte NADPH oxidase to produce superoxide. In humans, inactivation of either of the components of the core of phagocyte NADPH oxidase, p22phox and gp91phox, leads to a severe immune disorder known as chronic granulomatous disease (CGD). Although a mouse model of gp91phox deficiency has been described, the study of p22phox-dependent immune deficiency has been stifled by the lack of an animal model. However, Botond Banfi and colleagues, at the University of Iowa, Iowa City, have now identified the nmf333 mouse strain as the first animal model of p22phox-deficiency. Surprisingly, the nmf333 mice were found to have a severe balance disorder in addition to a CGD-like immune defect. Further investigation revealed that the balance disorder was caused by the aberrant development of gravity-sensing organs due to inactivation of an NADPH oxidase in the inner ear. These data led the authors to propose that development of the balance center in the inner ear is controlled by an NADPH oxidase and that patients with the form of CGD caused by a p22phox deficiency might have unrecognized symptoms of a balance disorder.

TITLE: Mutation of the Cyba gene encoding p22phox causes vestibular and immune defects in mice

AUTHOR CONTACT:
Botond Banfi
University of Iowa, Iowa City, Iowa, USA.
Phone: (319) 335-4228; Fax: (319) 335-4194; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=33835

METABOLIC DISEASE: How sweet ChREBP is: the role of ChREBP and LXR liver proteins in glucose sensing

The liver regulates the conversion of excess dietary carbohydrates, including glucose, into triglycerides, a primary building block of fat in animals. The protein ChREBP and members of the LXR family of proteins are important mediators of this process, although the precise mechanisms of their function are not clear. In a new study, Catherine Postic and her colleagues at the Institut Cochin, France, investigated the role of LXRs in glucose-mediated liver genes. They found that although glucose is necessary for ChREBP activity in the liver, LXR proteins were not required for the stimulation of glucose-sensing genes. The authors concluded that these findings may aid the development of therapies for lipid-metabolism and glucose dysfunction-related diseases. In an accompanying commentary, Masakazu Shiota and Mark Magnuson at Vanderbilt University School of Medicine, Nashville, explain how these findings convincingly contradict a recent study proposing that LXR proteins act as glucose sensors in the liver.

TITLE: ChREBP, but not LXRs, is required for the induction of glucose-regulated genes in mouse liver