Comparing the Bbs10 complete knockout phenotype with a specific renal epithelial knockout one highlights the link between renal defects and systemic inactivation in mice. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Cognard, Noëlle; Scerbo, Maria; Obringer, Cathy; Yu, Xiangxiang; Costa, Fanny; Haser, Elodie; Le, Dane; Stoetzel, Corinne; Roux, Michel; Moulin, Bruno; Dollfus, Hélène; Marion, Vincent
• Is Part Of: Cilia. Volume 4:Issue 1(2015)
• Page Start: 1
• Page End: 12
• Publication Date: 2015-12
• Subjects: Bardet–Biedl Syndrome -- Bbs10 -- Total knockout -- Retinal degeneration -- Obesity -- Renal epithelial-specific KO; Cilia and ciliary motion -- Periodicals; Cilia and ciliary motion -- Health aspects -- Periodicals; Cytology -- Periodicals; 571.67
• DOI: 10.1186/s13630-015-0019-8
• Languages: English
• ISSNs: 2046-2530

Abstract

Abstract Background Bardet–Biedl Syndrome (BBS) is a genetically heterogeneous ciliopathy with clinical cardinal features including retinal degeneration, obesity and renal dysfunction. To date, 20 BBS genes have been identified withBBS10 being a majorBBS gene found to be mutated in almost 20 percent of all BBS patients worldwide. It codes for the BBS10 protein which forms part of a chaperone complex localized at the basal body of the primary cilium. Renal dysfunction in BBS patients is one of the major causes of morbidity in human patients and is associated initially with urinary concentration defects related to water reabsorption impairment in renal epithelial cells. The aim of this study was to study and compare the impact of a totalBbs10 inactivation (Bbs10 −/ − ) with that of a specific renal epithelial cells inactivation (Bbs10 fl/fl ; Cdh16 -Cre +/ − ). Results We generated theBbs10 −/ − and Bbs10 fl/fl ; Cadh16 -Cre +/ − mouse model and characterized them.Bbs10 −/ − mice developed obesity, retinal degeneration, structural defects in the glomeruli, polyuria associated with high circulating arginine vasopressin (AVP) concentrations, and vacuolated, yet ciliated, renal epithelial cells. On the other hand, theBbs10 fl/fl ; Cadh16 -Cre +/ − mice displayed no detectable impairment. Conclusions These data highlight the importance of a systemicBbs10 inactivation to trigger averted renal dysfunction whereas a targeted absence of BBS10 in the renal epithelium is seemingly non-deleterious.