Nephritis - Mouse Immune Complex Glomerulonephritis Induced by Cationic BSA

Membranous nephropathy (MN) is one of the most common causes of nephrotic syndrome in humans. MN is characterized by inflammation and renal failure, including proteinuria from the accumulation of immune complexes along the glomerular basement membrane (GBM). Chen et al. reported that immunizing mice with cationic BSA (cBSA) induces MN by depositing cBSA-IgG immune complexes in the mouse kidney, which is known as immune complex glomerulonephritis (ICGN) (1)

Chondrex, Inc. provides cBSA and complete Freund’s adjuvant to induce the mouse ICGN model, as well as a Mouse Albumin Detection Kit to evaluate ICGN progression. Please see our Induction of Mouse ICGN by cBSA protocol for more details. 

The information on the mouse ICGN model in the Table of Contents below will help you understand ICGN and choose an appropriate disease model for your experiment. If you have any questions about the mouse ICGN model, please contact us at

Reagents For Inducing Mouse Immune Complex Glomerulonephritis

Chondrex, Inc. also offers Rat Anti-Glomerular Basement Membrane Nephritis Models. Please refer to the animal model menu for more information.

Table of Contents

  1. Protocol for Mouse ICGN 
  2. Disease Monitoring
  3. Principle of Mouse ICGN
  4. Background of ICGN

1. Protocol to Induce Mouse ICGN

ICGN can be induced in Balb/c or ICR mice, but not C57BL/6 mice. On day 0, mice receive 100 ΅g of cBSA (Cat # 9058). emulsified with an equal volume of complete Freund’s adjuvant containing 1 mg/ml M. tuberculosis (Cat # 7008). This initial immunization introduces the cBSA antigen to the mouse immune system and primes it to produce antibodies specific for cBSA. After 2 weeks, mice are challenged with 400 ΅g of cBSA through intravenous injection every other day, for a total of five cBSA challenges. 

Note: Balb/c mice may develop anaphylactic shock. The injection on day 14 should be 50 ΅g instead of 400 ΅g, followed by 400 ΅g on days 16 to 22.

Figure 1. Inducing ICGN in Balb/c Mice

2. Disease Monitoring

To determine the severity of ICGN, Chondrex, Inc. recommends the Mouse Urinary Albumin Detection Kit (Cat # 3012). Mouse kidneys leak serum components, such as bilirubin, resulting in overestimated urinary protein levels if assayed using the turbidity method. Thus, proteinuria may not be a suitable marker to evaluate nephritis severity. On the other hand, albumin is typically the first protein observed in urine when kidney dysfunction develops. In the Mouse ICGN model, a mouse is deemed nephritic if the total albumin content in a 16-hour urine collection is greater than 1 mg, but urinary albumin levels may reach as high as 50-200 mg in a 16-hour urine collection depending on the severity of nephritis.

3. Principle of Mouse ICGN

Human MN is caused by the accumulation of immune complexes in the subepithelial space along the GBM. The deposited immune complex activates complement, leading to GBM thickening. There are several suggested mechanisms of immune complex deposition. 

In the mouse ICGN model, mice are repeatedly immunized with cBSA. The positively charged cBSA binds to the GBM due to its negative charge. Anti-cBSA antibodies (predominantly IgG1) develop immune complexes with cBSA deposited on the GBM, leading to many symptoms seen in human MN: GBM thickening, hypoalbuminemia, and proteinuria. This pathogenesis of cBSA has been implicated in childhood MN (2).

4. Background of ICGN

Glomerulonephritis refers to an array of immune-mediated diseases that result in inflammation of the glomerulus, the filtering components of the kidneys. MN and membranous glomerulonephritis, are the most common causes of nephrotic syndrome in humans. MN is characterized by the accumulation of immune-complexes along the GBM. The deposition of immune complexes thickens the GBM and activates complement. The activated inflammatory cascades result in compromised kidney function, including proteinuria and eventual renal failure. 

Previous studies have used an autoimmune rat MN model (3), Heymann nephritis, to understand human MN pathology. While Heymann nephritis recapitulates many aspects of human MN, there are drawbacks to using a rat model. Mouse models of MN are a valuable tool for studying MN pathogenesis and developing targeted therapeutics due to easy handling, and availability of mouse monoclonal antibodies and transgenic mouse strains. Wayne et al. demonstrated that administering cBSA in rabbits can induce membranous nephropathy symptoms (4). Additionally, ICGN animal models induced by cBSA injection have been successfully established in dogs (5), cats (6), and rabbits (4). Furthermore, Chen et al. applied this protocol to mice, which is known as mouse immune complex glomerulonephritis (ICGN) (1).


  1. Chen, J.S., et al., Mouse model of membranous nephropathy induced by cationic bovine serum albumin: antigen dose response relations and strain differences. Nephrol Dial Transplant 19(11):2721-8 (2004).
  2.  H. Debiec et al., Early-childhood membranous nephropathy due to cationic bovine serum albumin. N Engl J Med. 364, 2101–2110 (2011).
  3. Yamamoto, T., et al., Bovine serum albumin (BSA) nephritis in rats. I. Experimental model. Acta Pathol Jpn 28(6): p. 859-66 (1978).
  4. Bass, P.S., et al., The effect of cyclosporin A on cationized bovine serum albumin-induced nephropathy in NZW rabbits. J Pathol 167(1):41-7 (1992).
  5. Wright, N.G., et al., Experimental immune complex glomerulonephritis in dogs receiving cationized bovine serum albumin. Res Vet Sci 38(3):322-8 (1985).
  6. Nash, A.S., N.A. Mohammed, and N.G. Wright, Experimental immune complex glomerulonephritis and the nephrotic syndrome in cats immunised with cationised bovine serum albumin. Res Vet Sci 49(3):370-2 (1990).


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