| Research Abstract |
We employed mouse molecular genetic approaches and overexpressed human megsin gene in mice. Some megsin transgenic mice exhibited glomerular morphological changes at 40 weeks of age. The pathological changes included increased number of cells in the mesangial area and an expansion of mesangial matrix. Furthermore, when we induced anti-glomerular basement membrane (GBM) nephritis in wild type and megsin transgenic mice, mesangial expansion persisted only in the transgenic mice. The glomerular lesions in megsin transgenic mice were accompanied by an augmented immune complex deposition together with immunoglobulins and complement. It is unlikely that a primary mechanism of immune complex (IC) deposition in these mice was augmented production, because the levels of circulating IC in transgenic mice were at best trivial. The explanation of this phenomenon should be found in a decreased capacity of mesangial cells to clear macromolecules such as immune complexes. We speculate that overexpression of megsin, a mesangium predominant gene, might lead to mesangial dysfunction, impair the degradation and disposal of IC, and alter the microenvironment of mesangial matrix. We performed hemi-nephrectomy to accelerate glomerular injury in megsin transgenic mice. Hemi-nephrectomized transgenic mice developed focal segmental mesangial expansion, which was associated with proteinuria. Hemi-nephrectomized model of this transgenic mice might serve as a tool to investigate mechanisms of glomerular disease.
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