Establishment of a mouse IgA nephropathy model with the MBP-20-peptide fusion protein

Abstract

Here, we aimed to determine whether immunoglobulin-A nephropathy (IgAN) could be induced in Balb/c mice by immunizing them with a fusion protein (MBP-20 peptide) comprising the maltose-binding protein (MBP) and a 20-amino-acid peptide derived from Staphylococcus aureus. A recombinant plasmid encoding the fusion protein was constructed and expressed in bacterial cells. The synthetic 20-peptide was used to prepare the monoclonal antibody. Balb/c mice were immunized with the MBP-20-peptide fusion protein over a 21-week course before renal histology was examined at the light and electron microscopic levels. Direct immunofluorescence staining with the anti-20-peptide monoclonal antibody was also performed using renal biopsy tissue from human IgAN patients as a comparison. IgA and IgG specific for the 20-peptide in human and mice serum were detected. The IgAN experimental mice developed a clinical and pathological profile that closely resembled that of human IgAN patients, including the induction of hematuria and numerous histopathological features. Levels of IgA and IgG specific for the 20-peptide were significantly increased in serum from the IgAN experimental mice and IgAN patients compared with control mice and non-IgAN patients. In IgAN model mice, the anti-20-peptide antibody labeled glomeruli, while the antibody strongly labeled glomeruli and weakly labeled tubular epithelial cells in renal tissue from human IgAN patients. In conclusion, immunization with an MBP-20-peptide fusion protein is able to induce clinical and pathological features closely resembling IgAN in Balb/c mice, indicating a potentially useful role for the model in the study of IgAN and related diseases. © 2010 Wiley-Liss, Inc.