Comparing the Bbs10 complete knockout phenotype with a specific renal epithelial knockout one highlights the link between renal defects and systemic inactivation in mice.
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 with BBS10 being a major BBS 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 total Bbs10 inactivation (Bbs10 (-/-)) with that of a specific renal epithelial cells inactivation (Bbs10  (fl/fl) ; Cdh16-Cre (+/-)).


RESULTS
We generated the Bbs10 (-/-) 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, the Bbs10  (fl/fl) ; Cadh16-Cre (+/-)mice displayed no detectable impairment.


CONCLUSIONS
These data highlight the importance of a systemic Bbs10 inactivation to trigger averted renal dysfunction whereas a targeted absence of BBS10 in the renal epithelium is seemingly non-deleterious.
Ciliopathies Modeling and Associated Therapies Team, Laboratory of Medical Genetics, National Institute for Health and Medical Research (INSERM), U1112, Université of Strasbourg, 11 rue Humann, 67085 Strasbourg, France.|Service de Néphrologie-Transplantation, Nouvel Hôpital Civil, 1 place de l'Hôpital, 67091 Strasbourg, France.
Noëlle
N
Cognard
Ciliopathies Modeling and Associated Therapies Team, Laboratory of Medical Genetics, National Institute for Health and Medical Research (INSERM), U1112, Université of Strasbourg, 11 rue Humann, 67085 Strasbourg, France.
Maria J
MJ
Scerbo
Ciliopathies Modeling and Associated Therapies Team, Laboratory of Medical Genetics, National Institute for Health and Medical Research (INSERM), U1112, Université of Strasbourg, 11 rue Humann, 67085 Strasbourg, France.
Cathy
C
Obringer
Ciliopathies Modeling and Associated Therapies Team, Laboratory of Medical Genetics, National Institute for Health and Medical Research (INSERM), U1112, Université of Strasbourg, 11 rue Humann, 67085 Strasbourg, France.
Xiangxiang
X
Yu
Ciliopathies Modeling and Associated Therapies Team, Laboratory of Medical Genetics, National Institute for Health and Medical Research (INSERM), U1112, Université of Strasbourg, 11 rue Humann, 67085 Strasbourg, France.
Fanny
F
Costa
Ciliopathies Modeling and Associated Therapies Team, Laboratory of Medical Genetics, National Institute for Health and Medical Research (INSERM), U1112, Université of Strasbourg, 11 rue Humann, 67085 Strasbourg, France.
Elodie
E
Haser
Ciliopathies Modeling and Associated Therapies Team, Laboratory of Medical Genetics, National Institute for Health and Medical Research (INSERM), U1112, Université of Strasbourg, 11 rue Humann, 67085 Strasbourg, France.
Dane
D
Le
Ciliopathies Modeling and Associated Therapies Team, Laboratory of Medical Genetics, National Institute for Health and Medical Research (INSERM), U1112, Université of Strasbourg, 11 rue Humann, 67085 Strasbourg, France.
Corinne
C
Stoetzel
Institut Clinique de la Souris, Illkirch, 67400 Strasbourg, France.
Michel J
MJ
Roux
Service de Néphrologie-Transplantation, Nouvel Hôpital Civil, 1 place de l'Hôpital, 67091 Strasbourg, France.
Bruno
B
Moulin
Ciliopathies Modeling and Associated Therapies Team, Laboratory of Medical Genetics, National Institute for Health and Medical Research (INSERM), U1112, Université of Strasbourg, 11 rue Humann, 67085 Strasbourg, France.|Service de Génétique Médicale, Institut Génétique Médicale d'Alsace, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Hélène
H
Dollfus
Ciliopathies Modeling and Associated Therapies Team, Laboratory of Medical Genetics, National Institute for Health and Medical Research (INSERM), U1112, Université of Strasbourg, 11 rue Humann, 67085 Strasbourg, France.
Vincent
V
Marion
Bardet–Biedl Syndrome; Bbs10; Obesity; Renal epithelial-specific KO; Retinal degeneration; Total knockout