CD4+ T cell gene expression in B6 vs B6.Sle1c2 mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE31702 | GEO | 2011/08/30
SECONDARY ACCESSION(S): PRJNA145631
REPOSITORIES: GEO
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Project description:Sle1c is a sublocus of the NZM2410-derived Sle1 major susceptibility locus. We have previously shown that Sle1c contributes to lupus pathogenesis by conferring CD4+ T cell-intrinsic hyperactivation and increased susceptibility to chronic graft-versus-host disease (cGVHD) that mapped to the centromeric portion of the locus. In this study, we have refined the centromeric sublocus to a 675Kb interval, termed Sle1c2. Recombinant congenic strains expressing Sle1c2 exhibited a T cell-intrinsic CD4+ T cell hyperactivation and cGVHD susceptibility, similar to mice with the parental Sle1c. We performed a microarray analysis on CD4+ T cells to gain insights into the transcriptional programs that regulate the hyperactivation conferred by Sle1c2. CD4+ T cell cDNA was prepared from spenocytes from 5 mice from each strain and B6.Sle1c2 gene expression was compared to B6 gene expresion.
2011-08-29 | E-GEOD-31702 | biostudies-arrayexpress
Project description:Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic beta-cell destruction. It is a complex genetic trait driven by over 30 genetic loci with parallels between humans and mice. The NOD mouse spontaneously develops autoimmune diabetes and is widely used to identify insulin-dependent diabetes (Idd) genetic loci linked to diabetes susceptibility. While many Idd loci have been extensively studied, the impact of the Idd2 locus on autoimmune diabetes susceptibility remains to be defined. To address this, we generated a NOD congenic mouse bearing B10 resistance alleles on chromosome 9 in a locus coinciding with part of the Idd2 locus and find that NOD.B10-Idd2 congenic mice are highly resistant to diabetes. Bone marrow chimera and adoptive transfer experiments show that the B10 protective alleles provide resistance in an immune cell-intrinsic manner. While no T cell-intrinsic differences between NOD and NOD.B10-Idd2 mice were observed, we find that the Idd2 resistance alleles limit the formation of spontaneous and induced germinal centers. Comparison of the B cell transcriptome profile from NOD and NOD.B10-Idd2 mice reveal that resistance alleles at the Idd2 locus affect the expression of specific MHC molecules, a result confirmed by flow cytometry. Altogether, these data demonstrate that resistance alleles at the Idd2 locus impair germinal center formation and influence MHC expression, both of which likely contribute to reduce diabetes incidence.
2022-10-06 | GSE185487 | GEO
Project description:Autoimmune T follicular helper (Tfh) cells have different properties from B6/J nonautoimmune tfh cells. To compare differences in Tfh cells due to ongoing SLE disease, spontaneous splenic Tfh (CD4+CXCR5+PD-1+) were cell sorted from a pre-enriched population of negatively isolated total CD4 cells by autoMACS. New zealand derived triple congenic lupus strain was compared with B6/J. RNA was immediately extracted with no culturing or treatment of cells.
2018-05-01 | GSE106455 | GEO
Project description:We previously utilized interval-specific congenic lines derived from C57BL/6J (B6) and DBA/2J (D2) alleles to fine map a quantitative trait locus (QTL) influencing methamphetamine (MA)- induced locomotor activity. We identified a 0.23 MB critical interval on chromosome 11 containing only two protein coding genes, Rufy1 and Hnrnph1. Notably, Rufy1 contains three missense SNPs and Hnrnph1 contains 1 SNP near the 5’ UTR. In an effort to identify the molecular mechanisms that bridge genetic variation with behavior, we conducted transcriptome analysis via mRNA sequencing (RNA-seq) in a B6.D2 congenic line (chr.11: 50-60 Mb) that captures the QTL. There was an overrepresentation of cis-regulated, differentially expressed genes within the congenic interval (4 out of 92 differentially expressed genes; FDR < 0.05) and widespread genomic regulation on all autosomes.
2015-12-11 | GSE66366 | GEO
Project description:A C57BL6/J (B6) x CAST/Ei (CAST) strain intercross was used to identify the first mammalian QTL for macronutrient-specific intake (carbohydrate and fat) and for total energy intake. A region on proximal Chromosome 17 revealed two significant QTL that co-localized for increased macronutrient intake-carbohydrate (Mnic1) and total kilocalorie intake (Kcal2), adjusted for body weight. An interval-specific congenic strain, B6.CAST-17, was then developed which verified the QTL. A new sub-congenic strain was developed which retained the linked traits. Important new findings emerged shows that this congenic interval confers an activity phenotype, i.e., mice carrying the differential segment have 20% higher spontaneous physical activity levels compared with the host B6 strain. We hypothesize that this Chromosome 17 QTL is either encoded by a single gene locus that determines both food intake and physical activity, or by two or more genes, each determining a sub-phenotype of energy balance. Microarray analysis of skeletal muscle and hypothalamus in congenic and wild type B6 mice was carried out to identify potential candidate genes for the activity and food intake behavior. Keywords: macronutrient-specific intake, sub-congenic strain
2009-02-12 | GSE10517 | GEO
Project description:Nonobese diabetic (NOD) mice congenic for B10 derived genes in the Idd9 region of chromosome 4 are highly protected from the development of diabetes. In order to identify possible candidate genes within the Idd9 susceptibility region and possible downstream mediators of protection, we compared gene expression between NOD and Idd9 CD4+ T-cells. CD4+ T-cells with an activated phenotype (CD44-high/CD62L-low) were sorted from the pancreatic lymph nodes of female 8-week old mice. Mice were bred at Taconic farms and were line 905 (NOD.B10-Idd9 congenic) and line 6359 (NOD-like control strain with a B10 congenic region on chromosome 1 which does not modify diabetes incidence). Three replicate samples were prepared, each from four pooled pancreatic lymph nodes. CD4+CD44-highCD62L-low T-cells were sorted from each sample.
2012-02-01 | E-GEOD-35482 | biostudies-arrayexpress
Project description:Background and Aims: In the interleukin-10-deficient (Il10-/-) mouse model of IBD, 10 quantitative trait loci (QTL) have been shown to be associated with colitis susceptibility by linkage analyses on experimental crosses of highly susceptible C3H/HeJBir (C3Bir)-Il10-/- and partially resistant C57BL/6J (B6)-Il10-/- mice. The strongest locus (C3Bir-derived cytokine deficiency-induced colitis susceptibility [Cdcs]1 on Chromosome [Chr] 3) controlled multiple colitogenic subphenotypes and contributed the vast majority to the phenotypic variance in cecum and colon. This was demonstrated by interval-specific Chr 3 congenic mice wherein defined regions of Cdcs1 from C3Bir or B6 were bred into the IL-10-deficient reciprocal background and altered the susceptible or resistant phenotype. Furthermore, this locus likely acts by inducing innate hypo- and adaptive hyperresponsiveness, associated with impaired NFΚB responses of macrophages. The aim of the present study was to dissect the complexity of Cdcs1 by further development and characterization of reciprocal Cdcs1 congenic strains and to identify potential candidate genes in the congenic interval. Material and Methods: In total, 15 reciprocal congenic strains were generated from Il10-/- mice of either C3H/HeJBir or C57BL/6J backgrounds by 10 cycles of backcrossing. Colitis activity was monitored by histological grading. Candidate genes were identified by fine mapping of congenic intervals, sequencing, microarray analysis and a high-throughput real-time RT-PCR approach using bone marrow-derived macrophages. Results: Within the originally identified Cdcs1-interval, three independent regions were detected that likely contain susceptibility-determining genetic factors (Cdcs1.1, Cdcs1.2, and Cdcs1.3). Combining results of candidate gene approaches revealed Fcgr1, Cnn3, Larp7, and Alpk1 as highly attractive candidate genes with polymorphisms in coding or regulatory regions and expression differences between susceptible and resistant mouse strains. Conclusions: Subcongenic analysis of the major susceptibility locus Cdcs1 on mouse chromosome 3 revealed a complex genetic structure. Candidate gene approaches revealed attractive genes within the identified regions with homologs that are located in human susceptibility regions for IBD.
2009-10-01 | GSE15318 | GEO
Project description:Background and Aims: In the interleukin-10-deficient (Il10-/-) mouse model of IBD, 10 quantitative trait loci (QTL) have been shown to be associated with colitis susceptibility by linkage analyses on experimental crosses of highly susceptible C3H/HeJBir (C3Bir)-Il10-/- and partially resistant C57BL/6J (B6)-Il10-/- mice. The strongest locus (C3Bir-derived cytokine deficiency-induced colitis susceptibility [Cdcs]1 on Chromosome [Chr] 3) controlled multiple colitogenic subphenotypes and contributed the vast majority to the phenotypic variance in cecum and colon. This was demonstrated by interval-specific Chr 3 congenic mice wherein defined regions of Cdcs1 from C3Bir or B6 were bred into the IL-10-deficient reciprocal background and altered the susceptible or resistant phenotype. Furthermore, this locus likely acts by inducing innate hypo- and adaptive hyperresponsiveness, associated with impaired NFΚB responses of macrophages. The aim of the present study was to dissect the complexity of Cdcs1 by further development and characterization of reciprocal Cdcs1 congenic strains and to identify potential candidate genes in the congenic interval. Material and Methods: In total, 15 reciprocal congenic strains were generated from Il10-/- mice of either C3H/HeJBir or C57BL/6J backgrounds by 10 cycles of backcrossing. Colitis activity was monitored by histological grading. Candidate genes were identified by fine mapping of congenic intervals, sequencing, microarray analysis and a high-throughput real-time RT-PCR approach using bone marrow-derived macrophages. Results: Within the originally identified Cdcs1-interval, three independent regions were detected that likely contain susceptibility-determining genetic factors (Cdcs1.1, Cdcs1.2, and Cdcs1.3). Combining results of candidate gene approaches revealed Fcgr1, Cnn3, Larp7, and Alpk1 as highly attractive candidate genes with polymorphisms in coding or regulatory regions and expression differences between susceptible and resistant mouse strains. Conclusions: Subcongenic analysis of the major susceptibility locus Cdcs1 on mouse chromosome 3 revealed a complex genetic structure. Candidate gene approaches revealed attractive genes within the identified regions with homologs that are located in human susceptibility regions for IBD. Experiment Overall Design: Bone marrow derived macrophages (BMDM) of colitis susceptible C3Bir-Il10-/- and colitis resistant B6-Il10-/- as well as the Il10-/- reciprocal congenic strains CB-R1 (C3Bir genetic background carrying a long congenic chromosome 3 element containing Cdcs1 from B6, rendering this formerly susceptible background resistant) and BC-R3 (B6 genetic background that carries the Cdcs1-region of C3Bir) were cultured and stimulated with flagellin or left unstimulated. BMDM were obtained from 3 male mice per genotype and cultured in polystyrene 6-well culture plates. Before RNA-isolation, 3 wells per plate were stimulated with Cbir1 flagellin (and subsequently pooled for RNA isolation), the other 3 wells left unstimulated (and also pooled). In total, these experiments were replicated three times in order to perform microarray analyses in triplicates.
2009-10-09 | E-GEOD-15318 | biostudies-arrayexpress
Project description:Chronic graft versus host disease (cGVHD) is a systemic autoimmune-like syndrome. The role of Tph cells in the pathogenesis of cGVHD has not been examined, although previous studies have shown that cGVHD is characterized by loss of Tfh cells. Here, we show that in cGVHD patients and in a murine model that reflects characteristic features of human cGVHD, the proportions of Tph cells among CD4+ T cells in the blood were expanded. These cells augmented memory B cell differentiation and production of IgG via IL-21. Adoptive transfer experiments showed recirculation between Tph in the blood and tissue-resident T helper (Trh) cells in GVHD target tissues. The TCR repertoires of blood Tph cells and Trh cells in GVHD target tissues of mice were highly overlapping.
2023-02-22 | GSE200520 | GEO
Project description:Previously, using a forward genetic approach we identified B. burgdorferi arthritis-associated locus 1 (Bbaa1), a quantitative trait locus on Chr4, which physically encompasses the type I IFN gene cluster and regulates Lyme arthritis through heightened type I IFN production. Reciprocal radiation chimeras between B6.C3-Bbaa1 and B6 mice revealed that arthritis is initiated by radiation-sensitive cells, but orchestrated by radiation-resistant components of joint tissue. Advanced congenic lines were developed to reduce the physical size of the Bbaa1 interval, and RNA-seq of resident CD45- joint cells from advanced interval specific recombinant congenic lines (ISRCL4 and ISRCL3) identified myostatin as uniquely upregulated in association with Bbaa1 arthritis development. Our manuscript further demonstrates that myostatin expression is linked to IFN-β production, and in vivo inhibition of myostatin suppresses Lyme arthritis in the reduced interval Bbaa1 congenic mice, formally implicating myostatin as a novel downstream mediator of joint-specific inflammatory response to B. burgdorferi.
2018-02-13 | GSE102748 | GEO