CLUSTERIN KNOCKOUT MICE: AN EXPERIMENTAL MODEL OF IMMUNOTACTOID GLOMERULOPATHY?

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https://storage.unitedwebnetwork.com/files/1099/d6cd42e0afc9e3fb698ddedf2a16606a.pdf

Abstract Title

CLUSTERIN KNOCKOUT MICE: AN EXPERIMENTAL MODEL OF IMMUNOTACTOID GLOMERULOPATHY?

First Name *

XINGLAN

Last Name *

LI

Co-author 1

xingwei cai caixingwei@163.com Chengdu First People’s Hospital Anesthesia CHENGDU

Co-author 2

QIUNONG GUAN qguan@prostatecentre.com The University of British Columbia Urologic Sciences VANCOUVER

Co-author 3

JUNYA TANG y309642718@qq.com West China Hospital of Sichuan University Laboratory of pathology Chengdu

Co-author 4

XUDAN YANG yangxudan@med.uestc.edu.cn Sichuan Provincial People’s Hospital Pathology Chengdu

Co-author 5

TING CAI caiting@ucas.ac.cn Guoke Ningbo Life Science and Health Industry Research Institute Centre for Organ Protection Research NINGBO

Co-author 6

CAIGAN DU caigan@mail.ubc.ca The University of British Columbia Urologic Sciences VANCOUVER

Co-author 7

Co-author 8

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

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.

Methods

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.

Results

Here, 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.

Conclusions

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.

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