Faculty Collaboration Database

Inactivation of Bardet-Biedl syndrome genes causes kidney defects. Am J Physiol Renal Physiol 2011 Feb;300(2):F574-80

Date

11/26/2010

Pubmed ID

21106857

Pubmed Central ID

PMC3043995

DOI

10.1152/ajprenal.00150.2010

Scopus ID

2-s2.0-79551557954 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

Bardet-Biedl syndrome (BBS) is a rare hereditary autosomal recessive disease associated with several features including obesity, hypertension, and renal abnormalities. The underlying mechanisms of renal defects associated with BBS remain poorly defined. We examined the histological, molecular, and functional renal changes in BBS mouse models that have features of the human disorder. Interestingly, obese hypertensive Bbs4(-/-) mice exhibited inflammatory infiltration and renal cysts, whereas the obese normotensive Bbs2(-/-) mice had only minor inflammatory infiltration. Accordingly, the expression level of inducible nitric oxide synthase was elevated in the kidney of both BBS mice with a more marked increase in Bbs4(-/-) mice. In contrast, endothelial nitric oxide synthase expression was decreased in Bbs4(-/-), but not Bbs2(-/-), mice. Similarly, the expression levels of transient receptor potential vanilloid 1 and 4 channels as well as β- and γ-subunits of epithelial Na channel were significantly reduced only in the kidney of Bbs4(-/-) mice. Metabolic studies revealed changes in urine output and urinary concentrations of creatinine, blood urea nitrogen, sodium, and potassium with a more pronounced effect in Bbs4(-/-) mice. Finally, we found that calorie restriction which prevented obesity in BBS mice reversed the morphological and molecular changes found in Bbs2(-/-) and Bbs4(-/-) mice, indicating the kidney abnormalities associated with BBS are obesity related. These findings extend our understanding of the function of BBS proteins and emphasize the importance of these proteins in renal physiology.

Author List

Guo DF, Beyer AM, Yang B, Nishimura DY, Sheffield VC, Rahmouni K

Author

Andreas M. Beyer PhD Associate Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Bardet-Biedl Syndrome
Blood Urea Nitrogen
Caloric Restriction
Creatinine
Epithelial Sodium Channels
Female
Hypertension
Kidney
Male
Mice
Microtubule-Associated Proteins
Nitric Oxide Synthase Type III
Obesity
Oliguria
Potassium
Proteins
Sodium
TRPV Cation Channels