Figure 5.

Therapeutic effects of CLCN5 LV gene therapy

(A) Immunofluorescence analysis of megalin expression in mutant mice with and without CLCN5 LV delivery. Nuclei were stained with DAPI (shown in blue). Megalin signals are shown in red. (B) Quantitative analysis of tubular mean fluorescence intensity by ImageJ software. Each dot represents data from one tubule. Tubules from two kidneys (two sections per kidney) were analyzed. ∗p < 0.05 and ∗∗∗p < 0.0001 between the indicated two groups (Mann-Whitney test). (C) Effects of CLCN5 LV delivery on diuresis in mutant mice. (D) Effects of CLCN5 LV delivery on urinary calcium in mutant mice. (E) Effects of CLCN5 LV delivery on urinary protein in mutant mice. For (C)–(E), all mutant mice received 280 ng p24 of CLCN5 or ZsGreen LV to the left kidney at the age of 87 days. Data from each mouse are presented. The first data point is the time of LV injection and the pre-treatment urine parameters from urine samples were collected 37 days before LV injection. Post-treatment results are data from urine samples collected at the indicated ages. A dashed line indicates average values of wild-type male mice presented in Figure 1E. ∗p < 0.05 and ∗∗∗p < 0.001 compared with pre-treatment values (Dunn's multiple comparison test following Kruskal-Wallis test).