Establishment of a mouse IgA nephropathy model with the MBP-20-peptide fusion protein.
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.
Zhang
Lei
L
Department of Pathology, Harbin Medical University, Hei Longjiang Province, People's Republic of China.
Ye
Fei
F
He
Yan
Y
Kong
Dan
D
Han
Changsong
C
Zhao
Zhijie
Z
Zhu
Jiang
J
Meng
Hongxue
H
Liu
Xinghan
X
Jin
Xiaoming
X
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005920:Glomerular Mesangium / Q000276:immunology* / Q000473:pathology; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007116:Immunization, Passive; D008297:Male; D058619:Maltose-Binding Proteins / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000276:immunology*; D013211:Staphylococcus aureus / Q000378:metabolism
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D058619:Maltose-Binding Proteins; D010456:Peptides, Cyclic