Fig. 3.

Down-regulation of Bsnd in mouse recapitulates the human kidney phenotype. (A) Schematic showing the injection schedule of Cep290^Gt/Gt animals from a 129/Ola background. Mice were i.v. injected with an antisense oligonucleotide (ASO) targeted against the Bsnd gene, which codes for the CLC-type chloride channel accessory protein Barttin. (B) Western blot of murine kidney showing the reduction in Barttin protein level following knockdown with Bsnd ASO. (C) Immunofluorescence images of P21 mouse kidney from F2 Cep290^Gt/Gt animals on a 129/Ola background showing the expression of Arl13b (green) and Aqp2 (magenta) following injection of an ASO targeted against Bsnd. (Scale bars, 5 μm.) (D) Quantification of cilia tortuosity in Cep290^+/+ and Cep290^Gt/Gt animals (Student’s t test, *P < 0.05). (E) Immunofluorescence images showing the expression of Arl13b (green) and Aqp2 (magenta) in a section of a kidney biopsy from a Joubert syndrome patient (NPH621: G/G at rs2500341; SI Appendix, Table S1) with end-stage renal disease secondary to mutations in CEP290. (Scale bars, 10 μm.)