Journal article
Mutation of the Cyba gene encoding p22(phox) causes vestibular and immune defects in mice
The Journal of clinical investigation, Vol.118(3), pp.1176-1185
03/01/2008
DOI: 10.1172/JCI33835
PMCID: PMC2248803
PMID: 18292807
Abstract
In humans, hereditary inactivation of either p22(phox) or gp91(phox) leads to chronic granulomatous disease (CGD), a severe immune disorder characterized by the inability of phagocytes to produce bacteria-destroying ROS. Heterodimers of p22(phox) and gp9(phox) proteins constitute the superoxide-producing cytochrome core of the phagocyte NADPH oxidase. In this study, we identified the nmf333 mouse strain as what we believe to be the first animal model of p22(phox) deficiency. Characterization of nmf333 mice revealed that deletion of p22(phox) inactivated not only the phagocyte NADPH oxidase, but also a second cytochrome in the inner ear epithelium. As a consequence, mice of the nmf333 strain exhibit a compound phenotype consisting of both a CGD-like immune defect and a balance disorder caused by the aberrant development of gravity-sensing organs. Thus, in addition to identifying a model of p22(phox)-dependent immune deficiency, our study indicates that a clinically identifiable patient population with an otherwise cryptic loss of gravity-sensor function may exist. Thus, p22(phox) represents a shared and essential component of at least 2 superoxide-producing cytochromes with entirely different biological functions. The site of p22(phox) expression in the inner ear leads us to propose what we believe to be a novel mechanism for the control of vestibular organogenesis.
Details
- Title: Subtitle
- Mutation of the Cyba gene encoding p22(phox) causes vestibular and immune defects in mice
- Creators
- Yoko Nakano - University of IowaChantal M. Longo-Guess - Jackson LaboratoryDavid E. Bergstrom - Jackson LaboratoryWilliam M. Nauseef - University of IowaSherri M. Joness - E Carolina Univ, Dept Commun Sci & Disorders, Greenville, NC USABotond Banfi - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.118(3), pp.1176-1185
- Publisher
- Amer Soc Clinical Investigation Inc
- DOI
- 10.1172/JCI33835
- PMID
- 18292807
- PMCID
- PMC2248803
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Number of pages
- 10
- Grant note
- AI 34879-19; R01 AI034879; R56 AI034879 / NIAID NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R01 DC006443-03; R01 DC007431-02; R01 DC007431-03; R01 DC006443; R01 DC007431-01A1; R01 DC007431 / NIDCD NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Deafness & Other Communication Disorders (NIDCD) R01DC007431 / NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Deafness & Other Communication Disorders (NIDCD) I01 BX000513 / BLRD VA P30 DK-54759; P30 DK054759 / NIDDK NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) P30CA034196 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) I01BX000513 / Veterans Affairs; US Department of Veterans Affairs P30DK054759 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) P30 CA034196; CA034196 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R56AI034879 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Language
- English
- Date published
- 03/01/2008
- Academic Unit
- Anatomy and Cell Biology; Infectious Diseases; Otolaryngology; Internal Medicine
- Record Identifier
- 9984284345302771
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