Genetic Factors Regulating Experimental Arthritis in Mice and Rats

Wilder, Ronald L.; Remmers, Elaine F.; Kawahito, Yutaka; Gulko, Pércío S.; Cannon, Grant W.; Griffiths, Marie

doi:10.1159/000060492

Cited by 29 publications

(31 citation statements)

References 228 publications

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“…have also been documented to impact arthritis. More recently, DBA/1 loci conferring arthritis susceptibility have been identified (27,28). Mapping the responsible DBA/1 nephritis susceptibility loci may help identify shared genetic elements that subserve both types of end-organ disease in this strain.…”

Section: Discussionmentioning

confidence: 99%

Strain Distribution Pattern of Susceptibility to Immune-Mediated Nephritis

Xie

Sharma

Wang

et al. 2004

The Journal of Immunology

128

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The genetic basis of immune-mediated nephritis is poorly understood. Recent studies have demonstrated that the NZW mouse strain is more prone to immune-mediated nephritis compared with C57BL/6 and BALB/c strains. The present study extends these findings by challenging 12 additional inbred strains of mice with rabbit anti-mouse glomerular basement membrane (GBM) reactive sera. Compared with control sera-injected mice and anti-GBM-injected A/J, AKR/J, C3H/HeJ, DBA/2J, MRL/MpJ, NOD/LtJ, P/J, SJL/J, and SWR/J mice, the anti-GBM-injected BUB/BnJ, DBA/1J, and 129/svJ mice developed severe proteinuria and azotemia. Their kidneys exhibited pronounced glomerulonephritis, with crescent formation, as well as tubulointerstitial disease, with these phenotypes being particularly profound in 129/svJ mice. However, these strains did not appear to differ in the nature of their xenogeneic immune response to the administered rabbit sera, either quantitatively or qualitatively. Collectively, these findings allude to the presence of genetic elements in the BUB/BnJ, DBA/1J, and 129/svJ genomes that may potentially confer susceptibility to immune-mediated nephritis. Detailed studies to dissect out the immunological and genetic basis of renal disease in these three strains are clearly warranted.

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Section: Discussionmentioning

confidence: 99%

Strain Distribution Pattern of Susceptibility to Immune-Mediated Nephritis

Xie

Sharma

Wang

et al. 2004

The Journal of Immunology

128

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“…Because of this similarity in histology and immunopathology, CIA is now routinely used to validate new target systems for rheumatic disease therapy and to evaluate the efficacy of new drugs prior to clinical trials. There is substantial evidence that CIA is also very useful for identifying candidate genes that may predispose to RA and, perhaps, other genetically-related autoimmune diseases (3)(4)(5)(6).…”

mentioning

confidence: 99%

Identification of four new quantitative trait loci regulating arthritis severity and one new quantitative trait locus regulating autoantibody production in rats with collagen‐induced arthritis

Griffiths

Wang

Joe

et al. 2000

Arthritis & Rheumatism

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Objective. Collagen-induced arthritis (CIA) is a polygenic model of experimentally induced autoimmunity and chronic joint inflammation. This study maps genetic loci that regulate CIA susceptibility in DA/Bkl (DA) and BN/SsNHsd (BN) rats.Methods. Genome scans covering chromosomes 1-20 and interval mapping techniques using 159 simple sequence-length polymorphism markers were used to identify quantitative trait loci (QTLs) that regulate CIA in (DA ؋ BN)F 2 hybrids. Serum antibody titers to type II collagen were determined by enzyme-linked immunosorbent assay.Results. DA rats were high responders to porcine type II collagen (PII) and developed severe CIA (100%). BN rats were low responders to PII and resistant to CIA (0%). BN genes strongly repressed PII-induced CIA. Only 12% of (DA ؋ BN)F 1 rats (7 of 60) and 31% of (DA ؋ BN)F 2 rats (307 of 1,004) developed CIA. Three new QTLs (Cia11, Cia12, and Cia13) with significant logarithm of odds (LOD) scores of 5.6, 4.6, and 4.5, respectively, plus a suggestive QTL (Cia14*, LOD 3.0) regulating arthritis severity were identified on chromosomes 3, 12, 4, and 19. A new QTL, Ciaa3, associating with anticollagen antibody titer (antibody to PII LOD 6.5; antibody to rat type II collagen LOD 5.2) mapped to chromosome 9. Of 10 CIA QTLs previously identified in (DA ؋ F344) and (DA ؋ ACI) rats, only Cia1 in the major histocompatibility complex and a region coincident to Cia5 on chromosome 10 (LOD >8.0) influenced CIA severity in (DA ؋ BN)F 2 rats.Conclusion. Since CIA exhibits many of the pathologic features of rheumatoid arthritis, the data indicate that the variety of genetic elements regulating human autoimmune and rheumatic diseases may be much larger and more varied than originally envisioned.

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“…Arthritis can be induced with injections of type II collagen (collagen-induced arthritis, (CIA)) or proteoglycan combined with adjuvant oils, with complete Freund's adjuvant (adjuvant-induced arthritis, (AIA)), pristane (pristane-induced arthritis, (PIA)), squalene, incomplete Freund's adjuvant, 1 or by transfer of serum from K/B Â N TCR-transgenic mice. 29 Certain inbred strains of mice and rats are highly susceptible to these models, while other strains are resistant.…”

Section: Inducible Modelsmentioning

confidence: 99%

“…Susceptible strains typically develop symmetric and persistent arthritis with histologic characteristics that mimic those of RA. 1,[30][31][32] Disease onset can be timed with reasonable precision and specimens (serum, synovium, blood or lymphnode cells) collected in a systematic manner for functional studies or gene expression analysis during pre-clinical stages, early disease or chronic erosive stages.…”

Section: Inducible Modelsmentioning

confidence: 99%

“…(The reader is referred to several comprehensive reviews listing rat and mouse arthritis loci, their specific chromosome location, and more extensive details about the different models of arthritis). [1][2][3] Human studies and obstacles to the identification of RA susceptibility genes RA is a complex trait, and there is evidence for a strong MHC and non-MHC genetic component in its regulation. 4 Several susceptibility loci have been identified in family-based linkage studies, [5][6][7][8][9][10][11][12][13] yet until very recently none of those studies had led to the identification of new disease genes.…”

Section: Introductionmentioning

confidence: 99%

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Contribution of genetic studies in rodent models of autoimmune arthritis to understanding and treatment of rheumatoid arthritis

Gulko

2007

Genes Immun

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Rheumatoid arthritis (RA) is a chronic and potentially debilitating autoimmune disease. While novel therapies have emerged in recent years, disease remission is rarely achieved. RA is a complex trait, and the identifying of its susceptibility and severity genes has been anticipated to generate new targets for therapeutic intervention. However, finding those genes and understanding their function has been a challenging task. Studies in rodent intercrosses and congenics generated from inbred strains have been an important complementary strategy to identify arthritis genes, and understand how they operate to regulate disease. Furthermore, these new rodent arthritis genes will be new targets for therapeutic interventions, and will identify new candidate genes or candidate pathways for association studies in RA. In this review-opinion article I discuss RA genetics, difficulties involved in gene identification, and how rodent models can facilitate (1) the discovery of both arthritis susceptibility and severity genes, (2) studies of gene-environment interactions, (3) studies of gene-gender interactions, (4) epistasis, (5) functional characterization of the specific genes, (6) development of novel therapies and (7) how the information generated from rodent studies will be useful to understanding and potentially treating RA.

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Genetic Factors Regulating Experimental Arthritis in Mice and Rats

Cited by 29 publications

References 228 publications

Strain Distribution Pattern of Susceptibility to Immune-Mediated Nephritis

Strain Distribution Pattern of Susceptibility to Immune-Mediated Nephritis

Identification of four new quantitative trait loci regulating arthritis severity and one new quantitative trait locus regulating autoantibody production in rats with collagen‐induced arthritis

Contribution of genetic studies in rodent models of autoimmune arthritis to understanding and treatment of rheumatoid arthritis

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