Inactivation of Bardet-Biedl syndrome genes causes kidney defects
Open accessAbstract
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.
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Obesity is associated with several other changes in the kidney that promote the development of hypertension as well as chronic kidney disease and end-stage renal disease.
“Obesity is associated with several other changes in the kidney that promote the development of hypertension as well as chronic kidney disease and end-stage renal disease.”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [66]
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Nachury, M. V., Loktev, A. V., Zhang, Q., Westlake, C. J., Peränen, J., Merdes, A., Slusarski, D. C., Scheller, R. H., Bazan, J. F., Sheffield, V. C., et al. (2007) · Cell · doi:10.1016/j.cell.2007.03.053 · Cited by 1,384 · see citing works
Self-citationThe Ciliopathies: An Emerging Class of Human Genetic Disorders
Badano, J. L., Mitsuma, N., Beales, P. L., & Katsanis, N. (2006) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.7.080505.115610 · Cited by 1,144 · see citing works
The Cardinal Manifestations of Bardet–Biedl Syndrome, a Form of Laurence–Moon–Biedl Syndrome
Green, J. S., Parfrey, P. S., Harnett, J. D., Farid, N. R., Cramer, B. C., Johnson, G. J., Heath, O., McManamon, P. J., O'Leary, E., & Pryse-Phillips, W. E. M. (1989) · New England Journal of Medicine · doi:10.1056/nejm198910123211503 · Cited by 552 · see citing works
Nauli, S. M., Kawanabe, Y., Kaminski, J. J., Pearce, W. J., Ingber, D. E., & Zhou, J. (2008) · Circulation · doi:10.1161/circulationaha.107.710111 · Cited by 466 · see citing works
Nishimura, D. Y., Fath, M. A., Mullins, R. F., Searby, C. C., Andrews, M., Davis, R., Andorf, J. L., Mykytyn, K., Swiderski, R. E., Yang, B., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405496101 · Cited by 365 · see citing works
Self-citationMechanistic insights into Bardet-Biedl syndrome, a model ciliopathy
Zaghloul, N. A., & Katsanis, N. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37041 · Cited by 364 · see citing works
An incredible decade for the primary cilium: a look at a once-forgotten organelle
Davenport, J. R., & Yoder, B. K. (2005) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00118.2005 · Cited by 350 · see citing works
Mykytyn, K., Mullins, R. F., Andrews, M., Chiang, A. P.-F., Swiderski, R. E., Yang, B., Braun, T. A., Casavant, T. L., Stone, E. M., & Sheffield, V. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402354101 · Cited by 336 · see citing works
Self-citationMoore, S., Green, J. S., Fan, Y., Bhogal, A. K., Dicks, E. L., Fernandez, B. A., Stefanelli, M., Murphy, C., Cramer, B. C., Dean, J., et al. (2005) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30406 · Cited by 323 · see citing works
Role of Selective Leptin Resistance in Diet-Induced Obesity Hypertension
Rahmouni, K., Morgan, D. A., Morgan, G. M., Mark, A. L., & Haynes, W. G. (2005) · Diabetes · doi:10.2337/diabetes.54.7.2012 · Cited by 319 · see citing works
Self-citationStoetzel, C., Muller, J., Laurier, V., Davis, E. E., Zaghloul, N. A., Vicaire, S., Jacquelin, C., Plewniak, F., Leitch, C. C., Sarda, P., et al. (2006) · The American Journal of Human Genetics · doi:10.1086/510256 · Cited by 237 · see citing works
Leptin resistance contributes to obesity and hypertension in mouse models of Bardet-Biedl syndrome
Rahmouni, K., Fath, M. A., Seo, S., Thedens, D. R., Berry, C. J., Weiss, R. M., Nishimura, D. Y., & Sheffield, V. C. (2008) · Journal of Clinical Investigation · doi:10.1172/jci32357 · Cited by 227 · see citing works
Self-citationMajor contribution of tubular secretion to creatinine clearance in mice
Eisner, C. B., Faulhaber‐Walter, R., Wang, Y., Leelahavanichkul, A., Yuen, P. S. T., Mizel, D. E., Star, R. A., Briggs, J. P., Levine, M., & Schnermann, J. B. (2009) · Kidney International · doi:10.1038/ki.2009.501 · Cited by 189 · see citing works
Bardet-Biedl syndrome: an emerging pathomechanism of intracellular transport
Blacque, O. E., & Leroux, M. R. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6180-x · Cited by 186 · see citing works
Mkks-null mice have a phenotype resembling Bardet–Biedl syndrome
Fath, M. A., Mullins, R. F., Searby, C. C., Nishimura, D. Y., Wei, J., Rahmouni, K., Davis, R. E., Tayeh, M. K., Andrews, M., Yang, B., et al. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi123 · Cited by 185 · see citing works
Self-citationThe Spectrum of Renal Disease in Laurence–Moon–Biedl Syndrome
Harnett, J. D., Green, J. S., Cramer, B. C., Johnson, G. J., Chafe, L. L., McManamon, P. J., Farid, N. R., Pryse-Phillips, W. E. M., & Parfrey, P. S. (1988) · New England Journal of Medicine · doi:10.1056/nejm198809083191005 · Cited by 165 · see citing works
The role of transient receptor potential channels in kidney disease
Woudenberg-Vrenken, T. E., Bindels, R. J. M., & Hoenderop, J. G. J. (2009) · Nature Reviews Nephrology · doi:10.1038/nrneph.2009.100 · Cited by 141 · see citing works
Adipose depot-specific modulation of angiotensinogen gene expression in diet-induced obesity
Rahmouni, K., Mark, A. L., Haynes, W. G., & Sigmund, C. D. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00551.2003 · Cited by 121 · see citing works
Self-citationBenzinou, M., Walley, A. J., Lobbens, S., Charles, M.-A. A., Jouret, B., Fumeron, F., Balkau, B., Meyre, D., & Froguel, P. (2006) · Diabetes · doi:10.2337/db06-0337 · Cited by 96 · see citing works
Mechanisms mediating renal sympathetic activation to leptin in obesity
Morgan, D. A., Thedens, D. R., Weiss, R., & Rahmouni, K. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90324.2008 · Cited by 89 · see citing works
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Wang, Y., & Wang, D. H. (2005) · Hypertension · doi:10.1161/01.hyp.0000197390.10412.c4 · Cited by 74 · see citing works
Iannello, S., Bosco, P., Cavaleri, A., Camuto, M., Milazzo, P., & Belfiore, F. (2002) · Obesity Reviews · doi:10.1046/j.1467-789x.2002.00055.x · Cited by 67 · see citing works
do Carmo, J. M., Tallam, L. S., Roberts, J. V., Brandon, E. L., Biglane, J., da Silva, A. A., & Hall, J. E. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00187.2009 · Cited by 50 · see citing works
TNFR1-deficient mice display altered blood pressure and renal responses to ANG II infusion
Chen, C. C. A., Pedraza, P. L., Hao, S., Stier, C. T., & Ferreri, N. R. (2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00344.2010 · Cited by 47 · see citing works
Sympathetic activation in cardiovascular and renal disease
Grassi, G. M., Arenare, F., Pieruzzi, F., Brambilla, G., & Mancia, G. (2009) · Journal of Nephrology · doi:10.1093/joneph/22.2.190 · Cited by 44 · see citing works
Wang, D. H. (2008) · Current Opinion in Cardiology · doi:10.1097/hco.0b013e32830460ad · Cited by 18 · see citing works
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- Grassi G, 2009, J Nephrol, 22, 190
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Caterino, M., Zacchia, M., Costanzo, M., Bruno, G., Arcaniolo, D., Trepiccione, F., Siciliano, R. A., Mazzeo, M. F., Ruoppolo, M., & Capasso, G. (2018) · Kidney & Blood Pressure Research · doi:10.1159/000488096 · Cited by 31 · see citing works
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- Authors
- Guo, D.-F., Beyer, A. M., Yang, B., Nishimura, D. Y., Sheffield, V. C., & Rahmouni, K.
- Affiliations
- Departments of 1Internal Medicine,
- Obstetrics and Gynecology,
- Pediatrics and Genetics (US)
- University of Iowa (US)
- Corresponding author
- Rahmouni, Kamal
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 2011-02
- Volume
- 300
- Issue
- 2
- Pages
- F574-F580
- ISSN
- 1522-1466 (ISSN-L)
- 1931-857X
- PMC
- PMC3043995
- OpenAlex
- W2167250584
- Semantic Scholar
- 1a69513c32d709f41692479943757b559b857dc6
- Cited by
- 27
- References
- 26
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 2 · 2013: 2 · 2012: 2
- FWCI
- 0.72
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Renal Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Iowa Research Online (The University of Iowa) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Heart, Lung, and Blood Institute (5 T32-HL-07121-33, HL-084207, P01HL084207, T32HL007121)
- National Eye Institute (R01EY011298, EY011298, EY-017168, R01EY017168)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
- Keywords
- Bardet-Biedl syndrome, BBS4, BBS2, obesity, hypertension, renal cysts, inducible nitric oxide synthase, endothelial nitric oxide synthase, TRPV1, TRPV4, epithelial sodium channel, renal inflammation, caloric restriction, renal physiology, mouse model
- MeSH terms
- Animals, Blood Urea Nitrogen, Creatinine, Female, Hypertension, Kidney, Male, Microtubule-Associated Proteins, Obesity, Oliguria, Potassium, Proteins, Sodium, Bardet-Biedl Syndrome, Caloric Restriction, TRPV Cation Channels, Mice, Nitric Oxide Synthase Type III, Epithelial Sodium Channels
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