A new mouse experimental model of focal segmental glomerulosclerosis produced by the administration of polyclonal anti-mouse nephrin antibody

Objectives: Nephrin is a component of the slit diaphragm between podocyte foot processes. Deficiencies or mutations of nephrin protein result in the nephrotic syndrome in humans. This study was designed to establish a mouse model of nephrotic syndrome using rabbit IgG against mouse nephrin cDNA. Methods: Female New Zealand White rabbits were immunized 4 times every 2 weeks with 30μg expression vector containing mouse nephrin cDNA encoding full-length, the immunoglobulin (Ig)like 1-8 motifs or the fibronectin motif. After 8 weeks, rabbit IgG was purified, and 4 mg was administered to C57BL/6N mice. Urinary protein, serum albumin, serum total cholesterol, and kidney specimens were evaluated. Results: Administration of rabbit IgG induced by full-length mouse nephrin cDNA resulted in massive proteinuria in 18 C57BL/6N mice from days 1 to 14. Mouse serum albumin decreased on days 3 and 7, whereas serum total cholesterol increased on days 3, 7, and 14. Focal segmental glomerulosclerosis was observed in 9 mouse kidney specimens on days 7 to 28. Control rabbit IgG did not induce proteinuria or kidney disease in mice. Conclusion: We successfully established a new mouse model of focal segmental glomerulosclerosis with nephrotic syndrome.