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.

Intramammary response to modified intramammary devices.

Twenty-five cows in three experiments were used to evaluate the following intramammary devices: abraded surfaces; abraded and sulfur hexafluoride-coated; abraded, sulfur hexafluoride-coated, and weighted; and smooth surfaces and weighted. The objectives of the experiments were 1) to determine whether coating the abraded intramammary devices prevented amorphous deposits and bacterial adherence on the devices, 2) to determine whether addition of weight to devices increased the concentration of somatic cells in milk, and 3) to evaluate milk production and response of mammary epithelial cells to the devices. Milk SCC and NAGase (EC 3.2.1.30) from quarters fitted with devices were increased in quarter bucket and stripping milk, but increases were similar among all devices. Macrophages were the predominate cell type in quarter milk before insertion and neutrophils after insertion. Moderate to heavy deposits of amorphous material were observed on all devices, regardless of time residing in the gland. Approximately 50% of the devices were colonized after intramammary inoculation with Corynebacterium bovis. Milk production in control quarters and in quarters with devices were similar. Neither coating with sulfur hexafluoride nor addition of weight to devices reduced amorphous deposits or bacterial adherence or enhanced milk somatic cell response.