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Establishment of a Mouse IgA Nephropathy Model With the MBP‐20‐Peptide Fusion Protein
Author(s) -
Zhang Lei,
Ye Fei,
He Yan,
Kong Dan,
Han Changsong,
Zhao Zhijie,
Zhu Jiang,
Meng Hongxue,
Liu Xinghan,
Jin Xiaoming
Publication year - 2010
Publication title -
the anatomical record: advances in integrative anatomy and evolutionary biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.21225
Subject(s) - fusion protein , nephropathy , antibody , peptide , microbiology and biotechnology , biology , monoclonal antibody , recombinant dna , immunology , biochemistry , endocrinology , gene , diabetes mellitus
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. Anat Rec 293:1729–1737, 2010. © 2010 Wiley‐Liss, Inc.