2.50
Hdl Handle:
http://hdl.handle.net/10547/228922
Title:
Genetic susceptibility to experimental autoimmune glomerulonephritis in the wistar kyoto rat; Genetic susceptibility to experimental autoimmune glomerulonephritis in the wistar kyoto rat
Authors:
Reynolds, John; Cook, Paul R.; Behmoaras, Jacques; Smith, Jennifer; Bhangal, Gurjeet; Tadros, Susan; Tee, Jonathan; Salama, Alan D.; Evans, David J.; Aitman, Timothy J.; Cook, H. Terence; Pusey, Charles D.
Abstract:
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 α3 chain of type IV collagen [α3(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 α3(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.
Affiliation:
Imperial College London; Imperial College London; University of Bedfordshire; University of Bedfordshire
Citation:
Reynolds, J. et al (2012) 'Genetic susceptibility to experimental autoimmune glomerulonephritis in the wistar kyoto rat' Am. J. Pathol. 180 (5):1843-1851
Publisher:
Elsevier
Journal:
The American journal of pathology
Issue Date:
May-2012
URI:
http://hdl.handle.net/10547/228922
DOI:
10.1016/j.ajpath.2012.01.029
PubMed ID:
22445570
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/22445570
Type:
Article
Language:
en
ISSN:
1525-2191
Appears in Collections:
Cell and Cryobiology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorReynolds, Johnen_GB
dc.contributor.authorCook, Paul R.en_GB
dc.contributor.authorBehmoaras, Jacquesen_GB
dc.contributor.authorSmith, Jenniferen_GB
dc.contributor.authorBhangal, Gurjeeten_GB
dc.contributor.authorTadros, Susanen_GB
dc.contributor.authorTee, Jonathanen_GB
dc.contributor.authorSalama, Alan D.en_GB
dc.contributor.authorEvans, David J.en_GB
dc.contributor.authorAitman, Timothy J.en_GB
dc.contributor.authorCook, H. Terenceen_GB
dc.contributor.authorPusey, Charles D.en_GB
dc.date.accessioned2012-06-14T11:16:21Zen
dc.date.available2012-06-14T11:16:21Zen
dc.date.issued2012-05en
dc.identifier.citationReynolds, J. et al (2012) 'Genetic susceptibility to experimental autoimmune glomerulonephritis in the wistar kyoto rat' Am. J. Pathol. 180 (5):1843-1851en_GB
dc.identifier.issn1525-2191en
dc.identifier.pmid22445570en
dc.identifier.doi10.1016/j.ajpath.2012.01.029en
dc.identifier.urihttp://hdl.handle.net/10547/228922en
dc.description.abstractIn 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 α3 chain of type IV collagen [α3(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 α3(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.en_GB
dc.language.isoenen
dc.publisherElsevieren_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/22445570en_GB
dc.titleGenetic susceptibility to experimental autoimmune glomerulonephritis in the wistar kyoto raten
dc.titleGenetic susceptibility to experimental autoimmune glomerulonephritis in the wistar kyoto raten
dc.typeArticleen
dc.contributor.departmentImperial College Londonen_GB
dc.contributor.departmentImperial College Londonen_GB
dc.contributor.departmentUniversity of Bedfordshireen
dc.contributor.departmentUniversity of Bedfordshireen
dc.identifier.journalThe American journal of pathologyen_GB

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