Genetic linkage analysis of collagen-induced arthritis in the mouse

Jirholt, Johan; Cook, Andrew D.; Emahazion, Tesfai; Sundvall, Mats; Jansson, Liselotte; Nordquist, Niklas; Pettersson, Ulf; Holmdahl, Rikard

doi:10.1002/(sici)1521-4141(199810)28:10<3321::aid-immu3321>3.0.co;2-m

Cited by 82 publications

(61 citation statements)

References 29 publications

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“…Amd1 and Asm1 may be a common locus for the same etiology of these 2 kinds of diseases. This is also the first study to map a gene locus for susceptibility to spontaneous arthropathy in DBA/1 mice, Amd2, on chromosome 3 in the region of a DBA/1 (14,22) and other mouse and rat models (23)(24)(25). However, the region of Amd2 did not share any of the loci involving the MHC.…”

Section: Discussionmentioning

confidence: 86%

Accelerating effect of an MRL gene locus on the severity and onset of arthropathy in DBA/1 mice

Oishi¹,

Miyazaki²,

Mizuki³

et al. 2005

Arthritis & Rheumatism

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Objective. To analyze the influence of the genetic background of an arthritis-prone strain of mice, MRL, on the spontaneous development of arthropathy in DBA/1 mice, which histopathologically resembles enthesopathy in humans, and to clarify the strain-specific gene loci and their interactions that confer susceptibility to arthropathy.Methods. MRL, DBA/1, (MRL ؋ DBA/1)F 1 , and (MRL ؋ DBA/1)F 2 intercross mice were prepared, and the severity and onset of arthropathy of the ankle joints in individual mice were quantified (0-3 and 0-5 scale, respectively). A genome-wide scan of 271 male F 2 intercross mice with polymorphic microsatellite markers was performed.Results. Only male DBA/1, (MRL ؋ DBA/1)F 1 , and (MRL ؋ DBA/1)F 2 mice developed arthropathy. The macroscopic and histopathologic findings of arthropathy in the F 2 mice were similar to those in the parental DBA/1 mice, but the onset was significantly earlier. In the quantitative trait locus analysis of male F 2 mice, 1 susceptibility locus for both the severity and early onset of the disease in the region of an MRL allele, Amd1, was located at marker D10Mit259 (map position 40.0 cM), which was common to 1 of the sialadenitis susceptibility loci in MRL mice, Asm1. Another susceptibility locus for the severity and early onset of arthropathy in the region of a DBA allele, Amd2, was located at D3Mit46 (29.5 cM). These loci manifested an additive effect on the development of arthropathy.Conclusion. Arthropathy in DBA/1 mice is under the control of an allelic combination of gene loci, one of which is common to the locus for sialadenitis in MRL/ MpJ-lpr/lpr mice.

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Section: Discussionmentioning

confidence: 86%

Accelerating effect of an MRL gene locus on the severity and onset of arthropathy in DBA/1 mice

Oishi¹,

Miyazaki²,

Mizuki³

et al. 2005

Arthritis & Rheumatism

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“…We have found the original Cia5/Eae3 locus 13,14 to consist of three loci affecting separate phases of the progression of arthritis, which each interacted uniquely with loci on chromosome 15. Cia5 affects disease onset and early severity, whereas Cia21 and Cia22 affect the chronic/late phase of the disease.…”

Section: Discussionmentioning

confidence: 99%

Identification of epistasis through a partial advanced intercross reveals three arthritis loci within the Cia5 QTL in mice

et al. 2005

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Identification of genes controlling complex diseases has proven to be difficult; however, animal models may pave the way to determine how low penetrant genes interact to promote disease development. We have dissected the Cia5/Eae3 susceptibility locus on mouse chromosome 3 previously identified to control disease in experimental models of multiple sclerosis and rheumatoid arthritis. Congenic strains showed significant but small effects on severity of both diseases. To improve the penetrance, we have now used a new strategy that defines the genetic interactions. The QTL interacted with another locus on chromosome 15 and a partial advanced intercross breeding of the two congenic strains for eight generations accumulated enough statistical power to identify interactions with several loci on chromosome 15. Thereby, three separate loci within the original QTL could be identified; Cia5 affected the onset of arthritis by an additive interaction with Cia31 on chromosome 15, whereas the Cia21 and Cia22 affected severity during the chronic phase of the disease through an epistatic interaction with Cia32 on chromosome 15. The definition of genetic interactions was a prerequisite to dissect the Cia5 QTL and we suggest the partial advanced intercross strategy to be helpful also for dissecting other QTL controlling complex phenotypes.

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“…Since we previously observed that genotypes homozygous for the short GA 13 and GA 16 alleles or heterozygous GA 13 /GA 16 were associated to MS, we specifically examined these three genotypes in JRA patients. As can be seen from Figure 2, all the three genotypes were increased among the JRA patients, but only the heterozygous GA [13][14][15][16] genotype reached statistical significance (5% vs 1%; OR ¼ 3.9; 95% CI (1.4-11.6); P n ¼ 4 ¼ 0.036). Overall, JRA patients carried significantly more frequent two copies of 'short' alleles (GA 13 and/or GA 16 ) compared to healthy controls (10% vs 6%; OR ¼ 1.9; 95% CI (1.1-3.5); P n ¼ 2 ¼ 0.04).…”

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confidence: 86%

Genetic association between juvenile rheumatoid arthritis and polymorphism in the SH2D2A gene

et al. 2004

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T-cell-specific adapter protein (TSAd) involved in the negative control of T-cell activation is encoded by the SH2D2A gene. Our recent studies indicate that homozygosity for short (ie GA 13 and GA 16 ) alleles of the SH2D2A gene promoter is associated with development of multiple sclerosis. To study whether the same SH2D2A promoter polymorphism also contributes to the genetic susceptibility to develop juvenile rheumatoid arthritis (JRA), we examined 210 JRA patients and 558 healthy unrelated controls from Norway. The frequency of the short allele GA 13 was increased among the JRA patients compared to control (0.098 vs 0.05; P n ¼ 8 ¼ 0.042). There was a significant increased frequency of HLA-DRB1*08-positive patients carrying two copies of 'short' alleles GA 13 and/or GA 16 compared to healthy controls (16% vs 6%; P n ¼ 4 ¼ 0.016). Our data indicate that the 'short' alleles of the SH2D2A promoter could contribute to the genetic susceptibility to JRA.

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Genetic linkage analysis of collagen-induced arthritis in the mouse

Cited by 82 publications

References 29 publications

Accelerating effect of an MRL gene locus on the severity and onset of arthropathy in DBA/1 mice

Accelerating effect of an MRL gene locus on the severity and onset of arthropathy in DBA/1 mice

Identification of epistasis through a partial advanced intercross reveals three arthritis loci within the Cia5 QTL in mice

Genetic association between juvenile rheumatoid arthritis and polymorphism in the SH2D2A gene

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