Summary |
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Variant origin |
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Variant description |
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Phenotypes |
View phenotypes and curated references for all genotypes (concatenated display).
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Notes |
Homozygosity for C57BL/10-derived alleles at Cia10 and Cia5 results in severe arthritis.
Candidate Genes
Microarray gene expression analysis was used to identify candidate genes for QTLs associated with collagen-induced arthritis. RNA from inflamed paws of collagen-treated mice were used in the microarray analysis and compared to RNA from normal paws. 223 genes showed a four-fold or greater expression difference between inflamed and normal paws. Nine of these genes are located near previously identified arthritis severity/susceptibility QTLs and may be considered for candidates. Microarray gene chip technology was used to identify differentially expressed candidate genes for the arthritis QTL on mouse Chromosome 3 named Cia5. The Cia5 QTL microarray chip contains 163 genes found between 95.3 Mb and 109.7 Mb on mouse Chromosome 3. (This region spans markers D3Mit101 to D3Mit103.) Gene expression in lymph nodes, spleen, and paws was compared between the resistant Cia5 congenic and susceptible B10.RIII background strain. Animals were immunized with 100 ug of bovine CII at 12 weeks of age. Gene expression was evaluated at 0, 6, and 12 days after immunization. A total of 26 genes in the Cia5 locus were found to have significant expression differences (P<0.05) between the congenic and B10.RIII. These genes were found in 2 clusters corresponding to Cia21 and Cia22. Some notable candidate genes are described below. Mapping and Phenotype information for this QTL, its variants and associated markersJ:50472173 (B10.RIII x RIIIS/J)F2 intercross animals were used to map novel loci associated with collagen-induced arthritis. Both strains share the H-2r MHC locus. B10.RIII is extremely susceptible to collagen-induced arthritis with 80-100% of the animals developing severe arthritis approximately 35 days after induction of disease. RIIIS/J is resistant and does not develop arthritis after induction. 55% of (B10.RIII x RIIIS/J)F1 animals develop arthritis after induction, and 45% of (B10.RIII x RIIIS/J)F2 animals develop arthritis after induction with wide variability in degree of disease severity. There appears to be a dominant, sex-influenced mode of disease inheritance. Male animals are more susceptible to arthritis than female animals. 121 markers covering 78% of the mouse genome at an average spacing of 20 cM were typed for QTL analysis. Cia5 mapped to a region of chromosome 3 spanning 35.2 cM - 52.5 cM with a peak LOD score of 4.12 at D3Mit72 (39.7 cM). This locus was confirmed in an intercross using (B10.RIII x RIIIS/J)F2 x B10.RIII N4 backcross (N4I2) animals. B10.RIII-derived alleles contribute to recessively inherited disease susceptibility at this locus. Cia5 maps near loci for susceptibility to Theiler's murine encephalomyelitis virus (Tmevd2 at 46cM) and insulin dependent diabetes (Idd17 at 39 cM; Idd10 at 48. 5cM).A suggestive QTL, Cia10, mapped to a region of chromosome 13 spanning 51 cM - 72 cM with a peak LOD score of 3.13 approximately 4 cM distal to D13Mit72 (51 cM). B10.RIII-derived alleles also contribute to recessively inherited disease susceptibility at this locus. Animals homozygous for B10.RIII alleles at Cia10 and Cia5 develop the most severe disease phenotype. |
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References |
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 10/22/2024 MGI 6.24 |
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