Summary
Crescentic glomerulonephritis (CRGN) is a major cause of human kidney failure but the underlying mechanisms are not fully understood. Wistar Kyoto (WKY) rats are uniquely susceptible to CRGN following injection of nephrotoxic serum, whereas Lewis (LEW) rats are resistant. Our previous genetic studies of nephrotoxic nephritis (NTN), a form of CRGN induced by nephrotoxic serum, identified Fcgr3-rs and Jund as WKY genes underlying the two strongest quantitative trait loci for NTN phenotypes, Crgn1 and Crgn2 respectively. We also showed that introgression of WKY Crgn1 or Crgn2 individually into a LEW background did not lead to formation of glomerular crescents. We have now generated a bicongenic strain, LEW.WCrgn1,2, in which WKY Crgn1 and Crgn2 are both introgressed into the LEW genetic background, and show development of NTN phenotypes, including glomerular crescents, in LEW.WCrgn1,2 bicongenic rats. Further, we characterise macrophage function and glomerular cytokine profiles in this new strain. Additionally, we show that LEW.WCrgn1,2 are resistant to development of glomerular crescents following immunisation with recombinant rat α3(IV)NC1, the specific Goodpasture autoantigen located in the glomerular basement membrane, against which the immune response is directed. Our results show that the new bicongenic strain responds differently to two distinct experimental triggers of CRGN. This is the first time that CRGN has been induced on a normally resistant rat genetic background and identifies the LEW.WCrgn1,2 strain as a new, potentially valuable model of macrophage-dependent glomerulonephritis.
- Received March 6, 2013.
- Accepted August 14, 2013.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms.
Article navigation
Related articles
Cited by...
More in this TOC section
Similar articles
Subject collections
Other journals from The Company of Biologists
DMM and COVID-19
We are aware that the COVID-19 pandemic is having an unprecedented impact on researchers worldwide. The Editors of all The Company of Biologists’ journals have been considering ways in which we can alleviate concerns that members of our community may have around publishing activities during this time. Read about the actions we are taking at this time.
Please don’t hesitate to contact the Editorial Office if you have any questions or concerns.
Alessandro Bailetti is awarded the DMM Outstanding Paper Prize 2019
The annual prize is awarded to the first author of the paper that is judged by the journal’s editors to be the most outstanding contribution to the journal that year. Alessandro Bailetti's winning paper presents results that indicate a possible connection between E(Pc) and the Tip60 complex, and leukemia. Find out more about Alessandro and read the winning paper.
Find DMM online
We may not be meeting you in person this year, but we’re always here to chat about DMM and The Company of Biologists. Join the conversation over on Twitter, email us or catch Scientific Editor Julija Hmeljak at these upcoming virtual meetings:
MRC Human Genetics Unit (Virtual) Symposium: Aberrant Cell State Transitions in Human Disease
23-24 September
Genomic Imprinting – from Biology to Disease
28 September – 1 October
ZDMS Virtual webinar series
Throughout September – December
Interview - Pratibha Singh
First author Pratibha Singh discusses her intestinal injury model in mouse neonatal pups, the most significant challenge impacting her field of research and shares her thoughts on how to better support early-career researchers.
Call for papers - The RAS Pathway: Diseases, Therapeutics and Beyond
DMM invites you to submit original research for a special issue focused on targeting the RAS pathway. The submission deadline is 1 March 2021. Find out more and showcase your breakthrough research in this special collection.
It’s a time of turmoil for young scientists
“My students are my priority – they are on the brink of their careers.”
Dr Jodie Rummer (ARC Centre of Excellence for Coral Reef Studies at James Cook University) talks about the importance of her role as a supervisor in supporting graduate students and post docs financially, intellectually and emotionally during this period of uncertainty.