PMC:1860061 / 27668-34084 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/1860061","sourcedb":"PMC","sourceid":"1860061","source_url":"http://www.ncbi.nlm.nih.gov/pmc/1860061","text":"Acknowledgements\nThe authors wish to thank Ilona Klamfuss for animal care. This work was supported by a grant from the EU FP6 (MRTN-CT-2004-005693, EURO-RA).\n\nFigures and Tables\nFigure 1 Differentially expressed genes between collagen-induced arthritis (CIA) susceptible and resistant strains. Comparison of the gene expression between the DBA/1 and FVB/N strains was performed at four phases of CIA. Of the 22,000 screened genes, 509 were differentially expressed between both strains at one or more phases of CIA, including 361 genes at the naive control (NC) phase, 141 genes at post-immunisation (PI) phase, 184 genes at the onset of arthritis (OA) phase and 85 genes at the chronic arthritis (CA) phase. The Venn diagram indicates the number of overlapping genes differentially expressed at different phases of CIA.\nFigure 2 Differentially expressed genes in the DBA/1 strain during collagen-induced arthritis (CIA). Three experimental conditions, post-immunisation (PI), onset of arthritis (OA) and chronic arthritis (CA), were compared with naïve control (NC) to search for differentially expressed genes. (a) Venn diagram indicating the number of overlapping genes differentially expressed at three phases of CIA. (b) Hierarchical clustering of the 310 differentially expressed genes. The left panel shows the distribution of relative gene expression across the hierarchical tree structure. Rows represent individual genes; columns represent individual value of triplicate samples for each experimental group. Each cell in the matrix represents the expression level of a gene, with red and green indicating transcription levels above and below the normal values for that gene, respectively. Four sample groups are indicated above the expression matrix. Six basic gene clusters (clusters I to VI) were yielded by the analysis according to the gene expression pattern during CIA. The expression patterns of the gene cluster are graphed and the major biological activities for each cluster that were examined by functional clustering analysis are indicated on the right.\nFigure 3 Visualisation of all the chromosomal locations of the small-effect QTL identified in this study (blue bar) as well as 120 genes of interest from gene expression profiling (black letters). The positions of the 120 genes and the peak markers of the QTL were retrieved from Ensembl [30]. Confidence intervals of all the QTL were set as 40 Mb.\nTable 1 Experimental groups used for gene expression profiling\nGroup Treatment RNA source No. of mice CV (percentage)\nDBA/1_NC None LN from naive control DBA/1 3 22.8\nDBA/1_PI CFA + collagen II LN from DBA/1 at day 10 after immunisation 3 20.4\nDBA/1_OA CFA + collagen II LN from DBA/1 mice at day 35 after immunisation 3 21.7\nDBA/1_CA CFA + collagen II LN from DBA/1 mice at day 95 after immunisation 3 25.8\nFVB/N_NC None LN from naive control FVB/N 3 21.1\nFVB/N_PI CFA + collagen II LN from FVB/N at day 10 after immunisation 3 22.6\nFVB/N_OA CFA + collagen II LN from FVB/N mice at day 35 after immunisation 3 18.4\nFVB/N_CA CFA + collagen II LN from FVB/N mice at day 95 after immunisation 3 21.1\nCA, chronic arthritis; CFA; complete Freund's adjuvant; CV, coefficient of variation; LN, lymph node; NC, naive control; OA, onset of arthritis; PI, post-immunisation.\nTable 2 Summary of the small-effect QTL identified in this study\nLoci Chromosome Peak marker Position (Mb) P value Susceptibility allele Overlapping QTL in mouse models of RA Snyternic region linked to RA (linked marker)\n1a,b,c 5 D5Mit348 23,9 0.00691 DBA/1 Cia13\n2b 5 D5Mit425 119,1 0.04397 DBA/1 Cia14 22q11 (D22S264), 12p13-q24 (D12S95)\n3a,b,c 6 D6Mit14 145,7 0.00315 FVB/N 12p13-pter (D12S99)\n4a,b,c 7 D7Mit248 59,3 0.03250 DBA/1\n5a,c 10 D10Mit261 85,1 0.00647 DBA/1 Cia8 21q22-qter (D21S268), 10q22-23 (D10S2327)\n6b,c 11 D11Mit214 115,2 0.00521 DBA/1 Pgia7 17q21-q25 (D17S1301)\n7c 16 D16Mit138 45,4 0.01499 FVB/N 3q29-qter (D3S1311)\n8c 17 D17Mit197 18,3 0.02994 FVB/N\naIdentified in all F2 290 progeny. bIdentified in 76 C5+/+ F2 progeny. cIdentified in 133 C5+/- F2 progeny. QTL, quantitative trait loci; RA, rheumatoid arthritis.\nTable 3 Summary of the small-effect QTL candidate genes\nGene Chr. Position (Mb) Description Difference between DBA/1 and FVB/N strains Difference during CIA in DBA/1 strain\nPhase Fold changea Phase Fold changeb\nSteap4 5 7.9 STEAP family member 4 NC/PI/CA 12.9/7.1/-5.9 CA -8.3\nAdd1 5 33.6 Adducin 1 (alpha) NC/PI 5.1/3.3 CA -4.6\nWdr1 5 37.8 WD repeat domain 1 NC/PI/OA/CA 4.9/3.5/2.4/-3.2 CA -7.1\nCd38 5 43.1 CD38 antigen NC/PI 5.7/4.0 CA -3.6\nTgfbr3 5 106.2 Transforming growth factor, beta receptor III NC/PI/CA 8.7/6.9/-3.2 CA -3.9\nOas1a 5 120.1 2'-5' Oligoadenylate synthetase 1A NC -2.5 OA 2.7\nBaz1b 5 134.1 Bromodomain adjacent to zinc finger domain, 1B NC/PI 5.9/5.7 CA -6.7\nLfng 5 139.5 Lunatic fringe gene NC/PI/OA 8.8/4.6/2.5 CA -7.7\nGna12 5 139.7 Guanine nucleotide binding protein, alpha 12 NC/PI/OA 4.1/3.7/3.3 CA -3.5\n8430419L09Rik 6 135.2 RIKEN cDNA 8430419L09 gene NC/PI/OA 17.8/12.8/3.3 CA -4.2\nEtnk1 6 143.2 Ethanolamine kinase 1 NC/PI/OA 4.6/3.9/2.6 CA -5.6\nNnp1 10 78.05 Novel nuclear protein 1 NC 3.0 CA -3.5\nKpnb1 11 97.2 Karyopherin (importin) beta 1 NC/PI/OA/CA 12.1/7.3/3.2/-20 CA -50\nStat5a 11 100.9 Signal transducer and activator of transcription 5A NC/PI 5.3/3.0 CA -4.6\nPscd1 11 118.2 Pleckstrin homology, Sec7 and coiled-coil domains 1 NC/PI/OA/CA 4.7/3.6/2.4/-4 CA -11\nMapk8ip3 17 23.07 Mitogen-activated protein kinase 8 interacting protein 3 NC/PI 3.9/2.5 CA -3.1\nMapk14 17 26.8 Mitogen activated protein kinase 14 NC/PI/OA/CA 9.1/4.7/3.1/-14 CA -33.3\nA430107D22Rik 17 30.5 RIKEN cDNA A430107D22 gene NC 3.7 CA -5\nHspa1a 17 33 Heat shock protein 1A PI/CA -3.8/-4.6 PI/OA 3.8/5.4\nH2-Q10 17 33.5 Histocompatibility 2, Q region locus 10 NC/PI/OA/CA 3.3/4.2/2.5/5.3 CA -3\nGabbr1 17 35.1 Gamma-aminobutyric acid receptor 1 NC/PI 4.9/2.5 CA -6.3\naFold change calculated by comparing DBA/1 with FVB/N. bFold change calculated by comparing post-immunisation (PI), onset of arthritis (OA) and chronic arthritis (CA) with naive control (NC), respectively. Chr., chromosome; CIA, collagen-induced 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