In order to develop a model in mouse similar to anti- Thy-1 nephritis in the rat, we prepared sheep antiserum against SV40-transformed mouse mesangial (MES 13) cells. In vivo, the anti-mouse mesangial cell serum-treated mice showed severe azotemia that peaked at day 6 and proteinuria that peaked at day 8, in a dose-dependent fashion. Light microscopy and electron microscopy showed duplication of glomerular basement membranes, mesangiolysis, subendothelial and mesangial electron-dense deposits, and foot process effacement. Intraglomerular tuft cell number was significantly reduced at day 4 and there were increased numbers of apoptotic cells at days 2 and 4. SCID mice and mice lacking C3 manifested similar responses to anti-mouse mesangial cell serum, suggesting that T cells, B cells and complement are not required for glomerular injury in this model. In vitro, anti-mouse mesangial cell serum treated mesangial cells showed greater release of lactate dehydrogenase, decreased cell survival, and increased apoptotic cell death. Anti-mouse mesangial cell serum induces glomerulopathy characterized by mesangiolysis and mesangial cell apoptosis, and followed by cellular proliferation.

1.
Unanue ER, Dixon FJ: Experimental glomerulonephritis: Immunological events and pathogenetic mechanisms. Adv Immunol 1967;6: 1–90.
[PubMed]
2.
Okabayashi A, Kondo Y, Shigematsu H: Cellular and histopathologic consequences of immunologically induced experimental glomerulonephritis. Curr Top Pathol 1976;61:1–43.
[PubMed]
3.
Kondo Y: Experimental glomerulonephritis. Acta Pathol Jpn 1982;32:197–209.
4.
Rifai A: Experimental models for IgA-associated nephritis. Kidney Int 1987;31:1–7.
[PubMed]
5.
Furness PN, Harris K: An evaluation of experimental models of glomerulonephritis. Int J Exp Pathol 1994;75:9–22.
[PubMed]
6.
Masugi Y, Oami H, Aihara K, Hashimoto K, Hakozaki T: Renal and pulmonary vascular changes induced by Crotalaria spectabilis in rats. Acta Pathol Jpn 1965;15:407–415.
[PubMed]
7.
Masugi Y: Immunoelectron microscopic studies on local vascular changes after immunological tissue injuries – especially on the mechanism of nephrotoxic nephritis. Acta Pathol Jpn 1969;19:265–281.
[PubMed]
8.
Yaar M, Foidart JM, Brown KS, Rennard SI, Martin GR, Liotta L: The Goodpasture-like syndrome in mice induced by intravenous injections of anti-type IV collagen and antilaminin antibody. Am J Pathol 1982;107:79–91.
[PubMed]
9.
Wick G, Von der Mark H, Dietrich H, Timpl R: Globular domain of basement membrane collagen induces autoimmune pulmonary lesions in mice resembling human Goodpasture disease. Lab Invest 1986;55:308–317.
[PubMed]
10.
Nakamura A, Yuasa T, Ujike A, Ono M, Nukiwa T, Ravetch JV, Takai T: Fcgamma receptor IIB-deficient mice develop Goodpasture’s syndrome upon immunization with type IV collagen: A novel murine model for autoimmune glomerular basement membrane disease. J Exp Med 2000;191:899–906.
[PubMed]
11.
Cochrane CG, Koffler D: Immune complex disease in experimental animals and man. Adv Immunol 1973;16:185–264.
[PubMed]
12.
Gallo GR, Caulin-Glaser T, Emancipator SN, Lamm ME: Nephritogenicity and differential distribution of glomerular immune complexes related to immunogen charge. Lab Invest 1983;48:353–362.
[PubMed]
13.
Tsuchimoto M, Komoriya K, Koyama T, Hosoda K, Takeshita T, Naruchi T, Matsuura E, Yamamoto I: An experimental model of nephritis induced by calf serum injection in mice. Jpn J Pharmacol 1984;36:223–234.
[PubMed]
14.
Koyama A, Inage H, Kobayashi M, Ohta Y, Narita M, Tojo S, Cameron JS: Role of antigenic charge and antibody avidity on the glomerular immune complex localization in serum sickness of mice. Clin Exp Immunol 1986;64:606–614.
[PubMed]
15.
Harada K, Yamamoto T, Hara M, Kihara I: Antigenic association between kidney and thymocyte. Acta Pathol Jpn 1982;32:483–489.
[PubMed]
16.
Paul LC, Rennke HG, Milford EL, Carpenter CB: Thy-1.1 in glomeruli of rat kidneys. Kidney Int 1984;25:771–777.
[PubMed]
17.
Yamamoto T, Yamamoto K, Kawasaki K, Yaoita E, Shimizu F, Kihara I: Immunoelectron microscopic demonstration of Thy-1 antigen on the surfaces of mesangial cells in the rat glomerulus. Nephron 1986;43:293–298.
[PubMed]
18.
Bagchus WM, Hoedemaeker PJ, Rozing J, Bakker WW: Glomerulonephritis induced by monoclonal anti-Thy 1.1 antibodies: A sequential histological and ultrastructural study in the rat. Lab Invest 1986;55:680–687.
[PubMed]
19.
Kollias G, Evans DJ, Ritter M, Beech J, Morris R, Grosveld F: Ectopic expression of Thy-1 in the kidneys of transgenic mice induces functional and proliferative abnormalities. Cell 1987;51:21–31.
[PubMed]
20.
Yamamoto T, Wilson CB: Quantitative and qualitative studies of antibody-induced mesangial cell damage in the rat. Kidney Int 1987;32:514–525.
[PubMed]
21.
Cuthbertson RA, Klintworth GK: Transgenic mice – a gold mine for furthering knowledge in pathobiology. Lab Invest 1988;58:484–502.
[PubMed]
22.
Robbins J: Gene targeting: The precise manipulation of the mammalian genome. Circ Res 1993;73:3–9.
[PubMed]
23.
Jaisser F, Beggah AT: Transgenic models in renal tubular physiology. Exp Nephrol 1998;6:438–446.
[PubMed]
24.
Mayadas TN, Rosenkranz A, Cotran RS: Glomerular inflammation: use of genetically deficient mice to elucidate the roles of leukocyte adhesion molecules and Fc-gamma receptors in vivo. Curr Opin Nephrol Hypertens 1999;8:293–298.
[PubMed]
25.
Hebert MJ, Takano T, Papayianni A, Rennke HG, Minto A, Salant DJ, Carroll MC, Brady HR: Acute nephrotoxic serum nephritis in complement knockout mice: Relative roles of the classical and alternate pathways in neutrophil recruitment and proteinuria. Nephrol Dial Transplant 1998;13:2799–2803.
26.
Sheerin NS, Springall T, Carroll M, Sacks SH: Altered distribution of intraglomerular immune complexes in C3-deficient mice. Immunology 1999;97:393–399.
[PubMed]
27.
Decker T, Lohmann-Matthes ML: A quick and simple method for the quantitation of lactate dehydrogenase release in measurements of cellular cytotoxicity and tumor necrosis factor (TNF) activity. J Immunol Methods 1988;115:61–69.
28.
Ishiyama M, Tominaga H, Shiga M, Sasamoto K, Ohkura Y, Ueno K: A combined assay of cell viability and in vitro cytotoxicity with a highly water-soluble tetrazolium salt, neutral red and crystal violet. Biol Pharm Bull 1996;19:1518–1520.
[PubMed]
29.
Floege J, Johnson RJ, Gordon K, Iida H, Pritzl P, Yoshimura A, Campbell C, Alpers CE, Couser WG: Increased synthesis of extracellular matrix in mesangial proliferative nephritis. Kidney Int 1991;40:477–488.
30.
Johnson RJ, Iida H, Alpers CE, Majesky MW, Schwartz SM, Pritzi P, Gordon K, Gown AM: Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis: Alpha-smooth muscle actin is a marker of mesangial cell proliferation. J Clin Invest 1991;87:847–858.
31.
Johnson RJ, Lombardi D, Eng E, Gordon K, Alpers CE, Pritzl P, Floege J, Young B, Pippin J, Couser WG, et al.: Modulation of experimental mesangial proliferative nephritis by interferon-gamma. Kidney Int 1995;47:62–69.
[PubMed]
32.
Baker AJ, Mooney A, Hughes J, Lombardi D, Johnson RJ, Savill J: Mesangial cell apoptosis: The major mechanism for resolution of glomerular hypercellularity in experimental mesangial proliferative nephritis. J Clin Invest 1994;94:2105–2116.
33.
Shimizu A, Kitamura H, Masuda Y, Ishizaki M, Sugisaki Y, Yamanaka N: Apoptosis in the repair process of experimental proliferative glomerulonephritis. Kidney Int 1995;47:114–121.
34.
Sato T, van Dixhoorn MG, Schroeijers WE, Huizinga TW, Reutelingsperger CP, van Es LA, Daha MR: Apoptosis of cultured rat glomerular mesangial cells induced by IgG2a monoclonal anti-Thy-1 antibodies. Kidney Int 1996;49:403–412.
[PubMed]
35.
Sato T, van Dixhoorn MG, Schroeijers WE, van Es LA, Daha MR: Efficient induction of apoptosis in cultured rat glomerular mesangial cells by dimeric monoclonal IgA anti-Thy-1 antibodies. Kidney Int 1997;51:173–181.
[PubMed]
36.
Assmann KJ, Tangelder MM, Lange WP, Schrijver G, Koene RA: Anti-GBM nephritis in the mouse: severe proteinuria in the heterologous phase. Virchows Arch [A] 1985;406:285–299.
[PubMed]
37.
Shirato I, Hosser H, Kimura K, Sakai T, Tomino Y, Kriz W: The development of focal segmental glomerulosclerosis in masugi nephritis is based on progressive podocyte damage. Virchows Arch 1996;429:255–273.
[PubMed]
38.
Abbas AK, Lichtman AA, Pober JS: B Cell Activation and Antibody Production in Cellular and Molecular Immunology, ed 4. Philadelphia, Saunders, 2000.
39.
Yamamoto T, Wilson CB: Complement dependence of antibody-induced mesangial cell injury in the rat. J Immunol 1987;138:3758–3765.
40.
Unanue ER, Dixon FJ: Experimental glomerulonephritis: Participation of complement in nephrotoxic niphritis. J Exp Med 1964;119:965–982.
41.
Cochrane CG, Unanue ER, Dixon FJ: A role of polymorphonuclear leukocytes and complement in nephrotoxic nephritis. J Exp Med 1965;122:99–119.
42.
Unanue ER, Mardiney MR Jr, Dixon FJ: Nephrotoxic serum nephritis in complement intact and deficient mice. J Immunol 1967;98:609–617.
[PubMed]
43.
Couser WG, Stilmant MM, Jermanovich NB: Complement-independent nephrotoxic nephritis in the guinea pig. Kidney Int 1977;11:170–180.
[PubMed]
44.
Jermanovich N, Jones DB, Spitzer R: SEM of complement-independent nephrotoxic nephritis. Scan Electron Microsc 1980:365–371.
45.
Pilia PA, Boackle RJ, Swain RP, Ainsworth SK: Complement-independent nephrotoxic serum nephritis in Munich Wistar rats. Immunologic and ultrastructural studies. Lab Invest 1983;48:585–597.
[PubMed]
46.
Gonzalez-Cuadrado S, Lopez-Armada MJ, Gomez-Guerrero C, Subira D, Garcia-Sahuquillo A, Ortiz-Gonzalez A, Neilson EG, Egido J, Ortiz A: Anti-Fas antibodies induce cytolysis and apoptosis in cultured human mesangial cells. Kidney Int 1996;49:1064–1070.
[PubMed]
47.
Gonzalez-Cuadrado S, Lorz C, Garcia del Moral R, O’Valle F, Alonso C, Ramiro F, Ortiz-Gonzalez A, Egido J, Ortiz A: Agonistic anti-Fas antibodies induce glomerular cell apoptosis in mice in vivo. Kidney Int 1997;51:1739–1746.
[PubMed]
48.
Shirato I, Sakai T, Kimura K, Tomino Y, Kriz W: Cytoskeletal changes in podocytes associated with foot process effacement in Masugi nephritis. Am J Pathol 1996;148:1283–1296.
[PubMed]
You do not currently have access to this content.