PMID- 22445570
OWN - NLM
STAT- MEDLINE
DCOM- 20120806
LR  - 20220129
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 180
IP  - 5
DP  - 2012 May
TI  - Genetic susceptibility to experimental autoimmune glomerulonephritis in the 
      Wistar Kyoto rat.
PG  - 1843-51
LID - 10.1016/j.ajpath.2012.01.029 [doi]
AB  - In experimental autoimmune glomerulonephritis (EAG), a model of Goodpasture's 
      disease, Wistar Kyoto (WKY) rats immunized with collagenase-solubilized 
      glomerular basement membrane (GBM) or the recombinant NC1 domain of the alpha3 chain 
      of type IV collagen [alpha3(IV)NC1] develop anti-GBM antibodies and focal necrotizing 
      glomerulonephritis with crescent formation. However, Lewis (LEW) rats, which 
      share the same major histocompatibility complex (MHC) haplotype, are resistant to 
      EAG development. A genome-wide linkage analysis of backcrossed animals with EAG 
      revealed a major quantitative trait locus (QTL) on rat chromosome 13 (LOD = 3.9) 
      linked to the percentage of glomerular crescents. To investigate the role of this 
      QTL in EAG induction, reciprocal congenic rats were generated (LEW.WCrgn1 
      congenic and WKY.LCrgn1 congenic), immunized with recombinant rat alpha3(IV)NC1, and 
      assessed for EAG development. WKY.LCrgn1 rats showed a marked reduction in 
      albuminuria, severity of crescentic nephritis, and number of glomerular 
      macrophages compared with WKY controls. No reduction in antibody levels was 
      observed. However, LEW.WCrgn1 rats were resistant to EAG development, as were LEW 
      controls. Macrophage activation in vitro was assessed in parental and congenic 
      rat bone marrow-derived macrophages (BMDMs). WKY.LCrgn1 BMDMs showed a 
      significant reduction in Fc receptor-mediated oxidative burst, phagocytosis of 
      opsonised polystyrene beads, and LPS-induced levels of MCP-1 secretion and iNOS 
      mRNA expression compared with WKY rats. These results confirm the importance of 
      Crgn1 on chromosome 13 in EAG susceptibility, mediated partly through differences 
      in Fc receptor-mediated macrophage activation.
CI  - Copyright (c) 2012 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Reynolds, John
AU  - Reynolds J
AD  - Renal Section, Department of Medicine, Imperial College London, Hammersmith 
      Campus, London, United Kingdom. john.reynolds@imperial.ac.uk
FAU - Cook, Paul R
AU  - Cook PR
FAU - Behmoaras, Jacques
AU  - Behmoaras J
FAU - Smith, Jennifer
AU  - Smith J
FAU - Bhangal, Gurjeet
AU  - Bhangal G
FAU - Tadros, Susan
AU  - Tadros S
FAU - Tee, Jonathan
AU  - Tee J
FAU - Salama, Alan D
AU  - Salama AD
FAU - Evans, David J
AU  - Evans DJ
FAU - Aitman, Timothy J
AU  - Aitman TJ
FAU - Cook, H Terence
AU  - Cook HT
FAU - Pusey, Charles D
AU  - Pusey CD
LA  - eng
GR  - G0400116/MRC_/Medical Research Council/United Kingdom
GR  - MC_U120061454/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120322
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Collagen Type IV)
RN  - 0 (Receptors, Fc)
RN  - 0 (Recombinant Proteins)
RN  - 0 (type IV collagen alpha3 chain)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Animals
MH  - Animals, Congenic
MH  - Anti-Glomerular Basement Membrane Disease/*genetics/immunology/pathology
MH  - Autoantibodies/biosynthesis
MH  - Autoantigens/immunology
MH  - Chemokine CCL2/biosynthesis
MH  - Collagen Type IV/immunology
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - Glomerular Basement Membrane/immunology
MH  - Kidney Glomerulus/pathology
MH  - Macrophage Activation/genetics
MH  - Macrophages/pathology
MH  - Male
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Phagocytosis/genetics/immunology
MH  - Phenotype
MH  - Quantitative Trait Loci/genetics
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Rats, Inbred WKY
MH  - Receptors, Fc/immunology
MH  - Recombinant Proteins/immunology
MH  - Respiratory Burst/genetics/immunology
MH  - Species Specificity
PMC - PMC3532591
EDAT- 2012/03/27 06:00
MHDA- 2012/08/07 06:00
PMCR- 2012/05/01
CRDT- 2012/03/27 06:00
PHST- 2011/08/19 00:00 [received]
PHST- 2012/01/03 00:00 [revised]
PHST- 2012/01/19 00:00 [accepted]
PHST- 2012/03/27 06:00 [entrez]
PHST- 2012/03/27 06:00 [pubmed]
PHST- 2012/08/07 06:00 [medline]
PHST- 2012/05/01 00:00 [pmc-release]
AID - S0002-9440(12)00164-2 [pii]
AID - AJPA821 [pii]
AID - 10.1016/j.ajpath.2012.01.029 [doi]
PST - ppublish
SO  - Am J Pathol. 2012 May;180(5):1843-51. doi: 10.1016/j.ajpath.2012.01.029. Epub 
      2012 Mar 22.