title: Mouse models of membranous nephropathy: the road less travelled by.
abstract: Membranous nephropathy (MN) is a major cause of idiopathic nephrotic syndrome in adults, often progressing to end-stage kidney disease. The disease is mediated by IgG antibodies that form subepithelial immune complexes upon binding to antigens expressed by podocytes or planted in the subepithelial space. Subsequent activation of the complement cascade, podocyte injury by the membrane attack complex and the expansion of the glomerular basement membrane cause proteinuria and nephrotic syndrome. The blueprint for our current understanding of the pathogenic mechanisms of MN has largely been provided by studies in rat Heymann nephritis, an excellent animal model that closely replicates human disease. However, further progress in this area has been hindered by the lack of robust mouse models of MN that can leverage the power of genetic approaches for mechanistic studies. This critical barrier has recently been overcome by the development of new mouse models that faithfully recapitulate the clinical and morphologic hallmarks of human MN. In these mouse models, subepithelial ICs mediating proteinuria and nephrotic syndrome are induced by injection of cationized bovine serum albumin, by passive transfer of heterologous anti-podocyte antibodies, or by active immunization with the NC1 domain of α3(IV) collagen. These mouse models of MN will be instrumental for addressing unsolved questions about the basic pathomechanisms of MN and also for preclinical studies of novel therapeutics. We anticipate that the new knowledge to be gained from these studies will eventually translate into much needed novel mechanism-based therapies for MN, more effective, more specific, and less toxic.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine Nashville, TN.
authors.forename: Dorin-Bogdan
authors.initials: DB
authors.lastname: Borza
authors.forename: Jun-Jun
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Beck
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyer-Schwesinger
authors.forename: Wentian
authors.initials: W
authors.lastname: Luo
keywords: Membranous nephropathy; anti-podocyte antibodies; glomerular basement membrane; immune complexes; mouse models; nephrotic syndrome; type IV collagen