Murine model of PLA2R-associated MN: the last brick in the 10 years wall
Recent animal studies demonstrated a pathogenic role of anti-THSD7A antibodies in the development of MN. The lack of endogenous PLA2R1 expression in rodents precluded analogous antibody transfer studies.
Take home messages:
- Transgenic mPLA2R-expressing mice demonstrated intact nephrin distribution with normal podocyte function
- Transfer of rabbit anti-mPLA2R antibodies to these mice induced nephrotic range proteinuria, hypercholesterolemia, and histomorphological signs of membranous nephropathy
- IHC/IF analyses revealed enhanced staining for mPLA2R in the presence of unaffected staining for mTHSD7A in the diseased mice
- These mice model are crucial to confirm the pathogenecity of anti-PLA2R autoantibodies and will help to better understand the pathomechanism of this disease, that can exploit new therapeutic approaches