Figure 5.

Reduced Severity of Glomerulonephritis and Arthritis by Kcnn4 Inactivation

(A) Glomerular immunohistochemistry showing the effect of specific Kcnn4 blocker TRAM-34 in renal injury in the WKY nephrotoxic nephritis model. Following nephrotoxic serum injection, glomerular crescents (PAS) and percentage of ED1+ macrophages were assessed in control (vehicle) and TRAM-34-treated rats (n = 4 rats were used per group of treatment). Original bars, 20 μm.

(B) Quantification of glomerular crescents, proteinuria, percentage of ED1⁺ cells and number of glomerular MGCs.

(C) Collagen antibody-induced arthritis (CAIA) was induced in 2-month-old male and female Kcnn4^−/− and Kcnn4^+/+ mice (mean ± SD; n = 12–15). Arthritic severity was monitored daily using a visual scoring system as detailed in Supplemental Experimental Procedures. Based on inflammation scoring, Kcnn4 deletion reduced inflammation in males and females, though the prevention was more efficient in female mice. From day 8 onward, the CAIA mean score is significantly different between Kcnn4^+/+ and Kcnn4^−/− animals for both genders (p < 0.001).

(D) Histopathomorphometry analysis of the paws and the ankles of Kcnn4^+/+ and Kcnn4^−/− naive and CAIA-induced female mice. All the histomorphometric parameters (inflammation, pannus, cartilage damage, and bone damage) were compared to CAIA Kcnn4^+/+ mice and are significant (mean ± SEM; n = 10–12 mice in each group; p < 0.05). Similar results were obtained in male mice (data not shown).

See also Figure S5.