A novel mouse model of phospholipase A2 receptor 1-associated membranous nephropathyámimics podocyte injury in patients

C Meyer-Schwesinger, NM Tomas, S Dehde, L Seifert… - Kidney International, 2020 - Elsevier
C Meyer-Schwesinger, NM Tomas, S Dehde, L Seifert, I Hermans-Borgmeyer, T Wiech…
Kidney International, 2020Elsevier
The phospholipase A2 receptor 1 (PLA2R1) is the major autoantigen in patients suffering
from membranous nephropathy. To date, the lack of endogenous glomerular expression of
PLA2R1 in mice and rats has impeded the establishment of PLA2R1-dependent animal
models of this disease. Here, we generated a transgenic mouse line expressing murine full-
length PLA2R1 in podocytes. Furthermore, expression of murine PLA2R1 did not result in
any morphological disturbance as high-resolution confocal microscopy demonstrated an …
The phospholipase A2 receptor 1 (PLA2R1) is the major autoantigen in patients suffering from membranous nephropathy. To date, the lack of endogenous glomerular expression of PLA2R1 in mice and rats has impeded the establishment of PLA2R1-dependent animal models of this disease. Here, we generated a transgenic mouse line expressing murine full-length PLA2R1 in podocytes. Furthermore, expression of murine PLA2R1 did not result in any morphological disturbance as high-resolution confocal microscopy demonstrated an intact nephrin distribution with normal foot processes. Transfer of rabbit anti-mPLA2R1 antibodies to these mice induced nephrotic range proteinuria, hypercholesterolemia, and histomorphological signs of membranous nephropathy. Immunohistochemical and immunofluorescence analyses revealed enhanced staining for murine PLA2R1 in the presence of unaffected staining for murine thrombospondin type-1 domain-containing 7A in the diseased mice, resembling what is classically found in patients with PLA2R1-associated membranous nephropathy Thus, our mouse model of membranous nephropathy will allow investigation of PLA2R1-specific pathomechanisms and may help to develop and assess antigen-specific treatments inávivo.
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