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Am J Clin Exp Immunol 2013;2(2):135-145
Review Article
Mouse models of membranous nephropathy: the road less travelled by
Dorin-Bogdan Borza, Jun-Jun Zhang, Laurence H Beck Jr, Catherine Meyer-Schwesinger, Wentian Luo
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN; Department of Nephrology, First
Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Medicine, Boston University School of
Medicine, Boston, MA; Department of Internal Medicine, Nephrology, University Medical Center Hamburg-Eppendorf,
Hamburg, Germany. These authors contributed equally to this work.
Received March 22, 2013; Accepted April 27, 2013; Epub June 15, 2013; Published June 30, 2013
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.
(AJCEI1303003).
Keywords: Membranous nephropathy, mouse models, immune complexes, nephrotic syndrome, anti-podocyte
antibodies, glomerular base-ment membrane, type IV collagen
Address correspondence to: Dr. Dorin-Bogdan Borza, S-3223 Medical Center North, Division of Nephrology, Vanderbilt
University Medical Center, 1161 21st Avenue South, Nashville, TN 37232-2372, USA. Phone: 615-322-4470; E-mail:
Bogdan.Borza@vanderbilt.edu; dbbor-za@gmail.com
Review Article
Mouse models of membranous nephropathy: the road less travelled by
Dorin-Bogdan Borza, Jun-Jun Zhang, Laurence H Beck Jr, Catherine Meyer-Schwesinger, Wentian Luo
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN; Department of Nephrology, First
Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Medicine, Boston University School of
Medicine, Boston, MA; Department of Internal Medicine, Nephrology, University Medical Center Hamburg-Eppendorf,
Hamburg, Germany. These authors contributed equally to this work.
Received March 22, 2013; Accepted April 27, 2013; Epub June 15, 2013; Published June 30, 2013
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.
(AJCEI1303003).
Keywords: Membranous nephropathy, mouse models, immune complexes, nephrotic syndrome, anti-podocyte
antibodies, glomerular base-ment membrane, type IV collagen
Address correspondence to: Dr. Dorin-Bogdan Borza, S-3223 Medical Center North, Division of Nephrology, Vanderbilt
University Medical Center, 1161 21st Avenue South, Nashville, TN 37232-2372, USA. Phone: 615-322-4470; E-mail:
Bogdan.Borza@vanderbilt.edu; dbbor-za@gmail.com
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