Comparison of gene expression between islets from NOD-Rag and NOD-Idd22 mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE206705 | GEO | 2022/06/27
REPOSITORIES: GEO
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Project description:Both immunodeficient and wild type NOD mice exhibit defects in control of early T-cell development in the thymus. We show that Rag1-deficient NOD mice fail to enforce both the b-selection checkpoint and an earlier T-cell commitment checkpoint, based on genome-wide genetic and transcriptome analyses. A major QTL peak for the checkpoint breakthrough phenotype mapped to the diabetes susceptibility Idd9/11 region, as confirmed by congenic mouse analysis. Genome-wide RNA deep-sequencing revealed two classes of differences between NOD and B6 Rag1-deficient thymocytes: first, effects of genetic background prior to breakthrough, and second, effects of the breakthrough itself. These genotypes differentially express numerous signal transduction genes, prominently tyrosine kinase and actin-binding genes, some located within QTL regions. Emerging NOD breakthrough cells depart from the expected DN3 phenotype by expressing many stem cell-associated proto-oncogenes, such as Lmo2, Hhex, Lyl1, and Kit which are normally repressed earlier, and by illegitimate activation of post-b-selection genes like Cd2, Cd5, and Cd4. Co-expression of stem cell and T-cell genes persists in thymic lymphoma cells that emerge with high penetrance in these mice. These results imply that NOD thymocytes have defects that can collapse regulatory boundaries at two early T-cell checkpoints, which may predispose them to leukemia and autoimmunity. Genetic and transcriptome analyses of early T-cell checkpoint failure and leukemia initiation in Rag1-deficient NOD mice
2013-03-07 | E-GEOD-40688 | biostudies-arrayexpress
Project description:Both immunodeficient and wild type NOD mice exhibit defects in control of early T-cell development in the thymus. We show that Rag1-deficient NOD mice fail to enforce both the b-selection checkpoint and an earlier T-cell commitment checkpoint, based on genome-wide genetic and transcriptome analyses. A major QTL peak for the checkpoint breakthrough phenotype mapped to the diabetes susceptibility Idd9/11 region, as confirmed by congenic mouse analysis. Genome-wide RNA deep-sequencing revealed two classes of differences between NOD and B6 Rag1-deficient thymocytes: first, effects of genetic background prior to breakthrough, and second, effects of the breakthrough itself. These genotypes differentially express numerous signal transduction genes, prominently tyrosine kinase and actin-binding genes, some located within QTL regions. Emerging NOD breakthrough cells depart from the expected DN3 phenotype by expressing many stem cell-associated proto-oncogenes, such as Lmo2, Hhex, Lyl1, and Kit which are normally repressed earlier, and by illegitimate activation of post-b-selection genes like Cd2, Cd5, and Cd4. Co-expression of stem cell and T-cell genes persists in thymic lymphoma cells that emerge with high penetrance in these mice. These results imply that NOD thymocytes have defects that can collapse regulatory boundaries at two early T-cell checkpoints, which may predispose them to leukemia and autoimmunity.
2013-03-07 | GSE40688 | 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:Gene expression in the islets of diseased NOD mice compared to congenic healthy NOD.B10 mice at various ages, during the progression of NOD disease.
2013-11-28 | GSE52815 | GEO
Project description:Comparison of gene expression between islets from NOD-Rag and NOD-Idd22 mice
| PRJNA851796 | ENA
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.
2012-02-01 | GSE35482 | GEO
Project description:Functional liability conferred by gene expression profile can be a possible basis for diseases phenotype. By comparing gene expression profiles in splenic T cells from NOD, C57BL/6 mice and their congenic strains with altered MHCs (NOD.H2^h4 , B6.NOD/Idd1,5/), we identified that the NOD splenic T cells have a strain dependent, tissue specific unique gene expression profile that can be but not necessarily be modulated by alternation of MHC. The NOD splenic T cells gene expression profile indicated a deregulated stress response system, especially heat shock protein family. We demonstrated that NOD splenic T cells have apoptosis defect in vivo and in vitro. Therefore, the gene expression profile may confer liability upon NOD splenic T cells to make them more susceptible to apoptosis, which can be a critical factor to lead to NOD lymphopenia. As recently described, compensatory homeostatic proliferation, driven by lymphopenia, generates autoimmunity in the NOD mouse. Keywords: other
2005-04-14 | GSE2524 | GEO
Project description:Functional liability conferred by gene expression profile can be a possible basis for diseases phenotype. By comparing gene expression profiles in splenic T cells from NOD, C57BL/6 mice and their congenic strains with altered MHCs (NOD.H2^h4 , B6.NOD/Idd1,5/), we identified that the NOD splenic T cells have a strain dependent, tissue specific unique gene expression profile that can be but not necessarily be modulated by alternation of MHC. The NOD splenic T cells gene expression profile indicated a deregulated stress response system, especially heat shock protein family. We demonstrated that NOD splenic T cells have apoptosis defect in vivo and in vitro. Therefore, the gene expression profile may confer liability upon NOD splenic T cells to make them more susceptible to apoptosis, which can be a critical factor to lead to NOD lymphopenia. As recently described, compensatory homeostatic proliferation, driven by lymphopenia, generates autoimmunity in the NOD mouse.
2010-06-10 | E-GEOD-2524 | 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:Type 1 Diabetes (T1D) in humans and the non-obese diabetic (NOD) mouse model results from autoreactive T cell destruction of pancreatic beta cells. A pathogenic role for B lymphocytes (B cells) in T1D first became evident when NOD mice made deficient in this population through introduction of an inactivated Igµ heavy chain gene (NOD.Igµnull) or chronic treatment with anti-IgM antibodies were strongly protected from disease. We produced an NOD background strain developing a greatly decreased T1D incidence due to a NOR-derived 44.31Mb congenic region from rs3674285 to D4Mit127 on distal Chr. 4 (termed NOD.NOR-Chr4 (NR4)) containing disease resistance alleles decreasing the pathogenic activity of autoreactive B cells. Microarrays were conducted on B cells purified from spleens of NOD and NR4 mice to highlight differentially expressed genes within the distal Chr. 4 locus. B cells were either cultured in media alone (unstimulated) or with BCR cross-linking anti-IgM-F(ab’)2 fragments (stimulated) for 2h before RNA was extracted for transcript analysis.
2012-06-08 | GSE37294 | GEO