Toward a bona fide animal model of PLA2R1-associated membranous nephropathy: one step forward

The major form of membranous nephropathy is characterized by autoantibodies to phospholipase A2 receptor 1 (PLA2R1). The study by Tomas et al. describes the first animal model where human PLA2R1 is ectopically expressed in mouse podocytes. Intriguingly, the transgenic mice spontaneously develop anti–human PLA2R1 antibodies and membranous nephropathy–like features, including immune deposits and nephrotic syndrome. The model raises questions about the spontaneous production of anti–human PLA2R1 antibodies and the additional steps to establish a bona fide animal model of membranous nephropathy. The major form of membranous nephropathy is characterized by autoantibodies to phospholipase A2 receptor 1 (PLA2R1). The study by Tomas et al. describes the first animal model where human PLA2R1 is ectopically expressed in mouse podocytes. Intriguingly, the transgenic mice spontaneously develop anti–human PLA2R1 antibodies and membranous nephropathy–like features, including immune deposits and nephrotic syndrome. The model raises questions about the spontaneous production of anti–human PLA2R1 antibodies and the additional steps to establish a bona fide animal model of membranous nephropathy. Podocyte expression of human phospholipase A2 receptor 1 causes immune-mediated membranous nephropathy in miceKidney InternationalVol. 103Issue 2PreviewAntibody-mediated autoimmune pathologies like membranous nephropathy are difficult to model, particularly in the absence of local target antigen expression in model organisms such as mice and rats; as is the case for phospholipase A2 receptor 1 (PLA2R1), the major autoantigen in membranous nephropathy. Here, we generated a transgenic mouse line expressing the full-length human PLA2R1 in podocytes, which has no kidney impairment after birth. Beginning from the age of three weeks, these mice spontaneously developed anti-human PLA2R1 antibodies, a nephrotic syndrome with progressive albuminuria and hyperlipidemia, and the typical morphological signs of membranous nephropathy with granular glomerular deposition of murine IgG in immunofluorescence and subepithelial electron-dense deposits by electron microscopy. Full-Text PDF