Abstract: TH-PO1086
New Animal Model of Non-HIV Collapsing Glomerulopathy
Session Information
- Glomerular Diseases: Podocyte Biology - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1204 Podocyte Biology
Authors
- Molina-Jijon, Eduardo, Rush University, Chicago, Illinois, United States
- Gambut, Stephanie, Rush Medical Center, Chicago, Illinois, United States
- Avila-Casado, Carmen, University Health Network, University of Toronto, Toronto, Ontario, Canada
- Clement, Lionel C., Rush University Medical Center, Chicago, Illinois, United States
- Del Nogal Avila, Maria, Rush University Medical Center, Chicago, Illinois, United States
- Chugh, Sumant S., Rush University Medical Center, Chicago, Illinois, United States
- Mace, Camille E., Rush University Medical Center, Chicago, Illinois, United States
Background
Collapsing glomerulopathy, usually classified as a form of focal and segmental glomerulosclerosis (FSGS), is the most severe and progressive form of glomerular disease. Most patients end up developing end stage kidney disease that requires dialysis or transplantation. There is presently no specific treatment for non-HIV collapsing glomerulopathy. Absence of animal models of non-HIV form of this disease was a problem in the past.
Methods
Transcriptional factor Zhx2 was overexpressed in rat podocytes under the control of the native human NPHS2 promoter. Two transgenic (TG) rat lines were generated: 142 and 144 which show increased expression of glomerular Zhx2 mRNA by 50.7% and 309.8% respectively. These 2 lines do not have any phenotype at baseline. We induced Adriamycin nephrosis, a model of FSGS, in wild type and heterozygous transgenic rats (7.5 mg of Adriamycin per kg/BW) and assessed for proteinuria and light microscopy at day 3 and 7 after injection. Different doses of Adriamycin (6.5 and 5.0 mg per kg/BW) were also injected in 144 transgenic rats, and studied at day 2, 5 and 9.
Results
TG 144 and TG 142 rats had significantly higher proteinuria than wild type rats following induction of Adriamycin nephrosis (7.5 mg per kg/BW). Renal histology in TG 144 rats on Day 7 revealed extensive glomerular collapse whereas no collapsing phenotype was noted in TG 142.
Injection of 6.5 and 5.0 mg of Adriamycin per kg/BW in TG 144 rats, induced significant proteinuria starting at day 5 and that still continue to rise at day 9. Light microscopy images show classic feature of collapsing glomerulopathy (Collapsed glomeruli, retraction, prominent VEC…) only in TG 144 rats injected with 6.5 mg. 144 TG rats injected with 5.0 mg dose show classic feature of FSGS.
Conclusion
ZHX2 transgenic rats injected with Adriamycin represent a new animal model of non-HIV collapsing glomerulopathy. Longitudinal glomerular gene expression analysis will be performed to study molecular mechanisms of development of the disease in wild type and ZHX2 144 TG rats at 6.5 mg per kg/BW dose.
Funding
- NIDDK Support