Abstract:

Objective To mimic the effects of structural changes of the hinge area of human IgA1 molecules on the pathogenesis of IgA nephropathy via a novel mouse model of spontaneous IgA nephropathy established by the transgenic method. Methods Sequences of the hinge area of wild type (transgenic group A) and O-glycan sites-mutated (transgenic group B) human IgA1 were inserted into the fertilized eggs of C57BL/6J mice by the transgenic method to replace the original sequences. Mice propagated based on genetic rules and genotype-positive mice were identified by PCR. The urine samples of positive parental mice at the age of 24 weeks and positive F1 mice at the age of 8 weeks were collected to conduct the property observation, microscopic examination of urinary sediment, and detection of the ratio of urine protein to urine creatinine. Renal tissues were harvested and IgA immunofluorescence staining and H-E staining were performed to assess the IgA deposition and histological changes of renal tissues. The blood was drawn from the heart of mice and the serum was isolated. Then IgA and IgG levels were detected. Results A total of 3 and 8 positive parental mice were obtained in transgenic group A and B, from which 17 and 52 positive F1 mice were obtained. The results of immunofluorescence staining indicated that IgA deposited in the glomerular mesangial area of kidneys of positive parental mice and positive F1 mice. The results of H-E staining showed mesenteric cell proliferation, increase of mesangial matrix, and inflammatory cell infiltration in mesenchyma. No erythrocytes were found in fresh urinary sediment by microscopic examination. The ratio of urine protein to urine creatinine and serum IgA and IgG levels of transgenic mice were significantly higher than those of wild type mice with the same age. Conclusion A mice model of IgA nephropathy is established by inserting sequences of the hinge area of human IgA1. Structural changes of the hinge area of IgA1 play a crucial role in the pathogenesis of IgA nephropathy.

Key words: IgA nephropathy, transgene, mouse, hinge area, glycosylation