Currently two Phospholipase A2 receptor (PLA2R)-specific experimental membranous nephritis models are established. In the one with mice, the complete human PLA2R is expressed specifically in podocytes, leading to the spontaneous development of PLA2R titer very early after birth. Consequently, granular immune complexes (green) and subepithelial electron-dense deposits are generated followed by severe proteinuria six weeks after birth (see graph). In a second model, a chimeric PLA2R consisting of human CysR-CTLD1, the most immunogenic part, and murine CTLD2-CTLD8, is specifically expressed in podocytes. This chimeric PLA2R expression is tolerated and therefore suitable for directed active immunisation using huPLA2R protein. After active immunisation, membranous nephropathy develops after 6 to 10 weeks including all expected features of the disease.

Using these models, we investigate the course of pathophysiology from disease initiation up to the end point of severe proteinuria including the still controversially discussed role of the complement system. Furthermore, both models are currently used to investigate highly specific therapies of different settings.