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Identification of multiple loci linked to inflammation and autoantibody production by a genome scan of a murine model of rheumatoid arthritis

1999; Wiley; Volume: 42; Issue: 12 Linguagem: Inglês

10.1002/1529-0131(199912)42

1529-0131

Jeffrey M. Otto, Gabriella Cs-Szab�, Jodi Gallagher, Sonja Velins, Katalin Mikecz, Edit I. Buz�s, Jill T. Enders, Yefu Li, Björn R. Olsen, Tibor T. Glant,

Glycosylation and Glycoproteins Research

Arthritis & RheumatismVolume 42, Issue 12 p. 2524-2531 Basic ScienceFree to Read Identification of multiple loci linked to inflammation and autoantibody production by a genome scan of a murine model of rheumatoid arthritis Jeffrey M. Otto, Corresponding Author Jeffrey M. Otto Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, IllinoisSection of Biochemistry and Molecular Biology, Departments of Biochemistry and Orthopedic Surgery, Rush–Presbyterian–St. Luke's Medical Center, 1653 West Congress Parkway, Chicago, IL 60612Search for more papers by this authorGabriella Cs-Szabó, Gabriella Cs-Szabó Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, IllinoisSearch for more papers by this authorJodi Gallagher, Jodi Gallagher Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, IllinoisSearch for more papers by this authorSonja Velins, Sonja Velins Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, IllinoisSearch for more papers by this authorKatalin Mikecz, Katalin Mikecz Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, IllinoisSearch for more papers by this authorEdit I. Buzás, Edit I. Buzás Semmelweis Medical University, Budapest, HungarySearch for more papers by this authorJill T. Enders, Jill T. Enders Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, IllinoisSearch for more papers by this authorYefu Li, Yefu Li Thomas Jefferson University, Philadelphia, PennsylvaniaSearch for more papers by this authorBjörn R. Olsen, Björn R. Olsen Harvard Medical School, Boston, MassachusettsSearch for more papers by this authorTibor T. Glant, Tibor T. Glant Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, IllinoisSearch for more papers by this author Jeffrey M. Otto, Corresponding Author Jeffrey M. Otto Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, IllinoisSection of Biochemistry and Molecular Biology, Departments of Biochemistry and Orthopedic Surgery, Rush–Presbyterian–St. Luke's Medical Center, 1653 West Congress Parkway, Chicago, IL 60612Search for more papers by this authorGabriella Cs-Szabó, Gabriella Cs-Szabó Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, IllinoisSearch for more papers by this authorJodi Gallagher, Jodi Gallagher Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, IllinoisSearch for more papers by this authorSonja Velins, Sonja Velins Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, IllinoisSearch for more papers by this authorKatalin Mikecz, Katalin Mikecz Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, IllinoisSearch for more papers by this authorEdit I. Buzás, Edit I. Buzás Semmelweis Medical University, Budapest, HungarySearch for more papers by this authorJill T. Enders, Jill T. Enders Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, IllinoisSearch for more papers by this authorYefu Li, Yefu Li Thomas Jefferson University, Philadelphia, PennsylvaniaSearch for more papers by this authorBjörn R. Olsen, Björn R. Olsen Harvard Medical School, Boston, MassachusettsSearch for more papers by this authorTibor T. Glant, Tibor T. Glant Rush University at Rush–Presbyterian–St. Luke's Medical Center, Chicago, IllinoisSearch for more papers by this author First published: 26 April 2001 https://doi.org/10.1002/1529-0131(199912)42:12 3.0.CO;2-0Citations: 55AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract Objective Proteoglycan-induced arthritis (PGIA) is a murine model of rheumatoid arthritis (RA), both in terms of its pathology and its genetics. PGIA can only be induced in susceptible murine strains and their F2 progeny. As with RA, the genetics are complex, containing both major histocompatibility complex (MHC)–related and non–MHC-related components. Our goal was to identify the underlying non–MHC-related loci that confer PGIA susceptibility. Methods We used 106 polymorphic markers to perform simple sequence-length polymorphism analysis on F2 hybrids of susceptible (BALB/c) and nonsusceptible (DBA/2) strains of mice. Because both strains of mice share the H2d haplotype, this cross permits identification and analysis of non–MHC-related genes. Results We identified a total of 12 separate quantitative trait loci (QTL) associated with PGIA, which we have named Pgia1 through Pgia12. QTLs associated with the inflammatory symptoms of PGIA were linked to chromosomes 7, 9, 15 (2 separate loci), 16, and 19. QTLs associated with autoantibody production were identified on chromosomes 1, 2, 7, 8, 10, 11, 16, and 18. QTLs on chromosomes 7 and 16 showed linkage to both inflammation and autoantibody production, suggesting a shared regulatory component in arthritis induction. The first inflammation QTL on chromosome 15 and the autoantibody QTL on chromosome 7 originate from the DBA/2 background, which indicates that as in RA, susceptibility genes can originate from heterogeneous backgrounds. Conclusion These data demonstrate the complexity of PGIA, where QTLs may be involved in multiple traits or even originate from a genetic background previously determined to be resistant. REFERENCES 1 Hasstedt SJ, Clegg DO, Ingles L, Ward RH. HLA-linked rheumatoid arthritis. Am J Hum Genet 1994; 55: 738– 46. 2 Hardwick LJ, Walsh S, Butcher S, Nicod A, Shatford J, Bell J, et al. Genetic mapping of susceptibility loci in the genes involved in rheumatoid arthritis. J Rheumatol 1997; 24: 197– 8. 3 Khan MA. Spondylarthropathies. Curr Opin Rheumatol 1994; 6: 351– 3. 4 David CS. The mystery of HLA-B27 and disease. 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