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Immunotactoid glomerulopathy (ITG) is one of clinicopathologic entities of glomerulonephritis and is characterized by glomerular deposits of electron dense microtubules, but its experimental model has not been identified. Clusterin (CLU) is a chaperone-like glycoprotein, and CLU knockout (KO) mice were initially found to develop age-dependent glomerulopathy with fibril deposit. The objective of study was to define the fibrillogenesis of the glomerulopathy in these mice.
Both wild type C57BL/6 (B6) and CLU-KO mice in B6 background (female and male, 10-24 months old) were used. The kidney specimens were sectioned for staining with hematoxylin and eosin, Masson-Trichrome and Congo-red. Immunohistochemistry was used for detecting the special antigens (IgG, DNAJB9), and transmission electron microscopy (TEM) for characterizing the fibril formation of the electron-dense mesangial deposits.
we showed that approximately 75% of glomeruli were affected with moderate to severe mesangial lesions in male CLU KO mice at the age of 24 months or 85% in female at 18 months, whereas WT mice exhibited little or no glomerular pathology at the similar age. Masson-Trichrome stain revealed fibrosis and immunocomplex in these mesangial lesions, in which Congo-red staining was weakly positive. The immuno-staining with anti-mouse IgG was positive but with anti-DNAJB9 negative. TEM confirmed that the electron-dense material in the mesangium was structured with hollow microtubules with approximately 50 nm diameter.
In conclusion, the glomerulopathy in CLU-KO mice were similar to that of ITG, implying that these mice may represent an experimental model of ITG and CLU may negatively regulate its fibrillogenesis.