Gene expression profiling in type 1 diabetes prone NOD mice immunized with a disease protective autoantigenic peptide

The early-life intestinal microbiota plays a key role in shaping host immune system development. We found that a single early-life antibiotic course (1PAT) accelerated type 1 diabetes (T1D) development in male NOD mice. The single course had deep and persistent effects on the intestinal microbiome, leading to altered cecal, hepatic, and serum metabolites. The exposure elicited sex-specific effects on chromatin states in the ileum and liver and perturbed ileal gene expression, altering normal maturational patterns. The global signature changes included specific genes controlling both innate and adaptive immunity. Microbiome analysis revealed four taxa each that potentially protect against or accelerate T1D onset, that were linked in a network model to specific differences in ileal gene expression. This simplified animal model reveals multiple potential pathways to understand pathogenesis by which early-life gut microbiome perturbations alter a global suite of intestinal responses, contributing to the accelerated and enhanced T1D development.

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Differential gene expression profiling of the sciatic nerve in type 1 and type 2 diabetic mice

Biomedical Reports ◽

10.3892/br.2018.1135 ◽

2018 ◽

Cited By ~ 3

Author(s):

Yu Gu ◽

Zhuo-Lin Qiu ◽

De-Zhao Liu ◽

Guo-Liang Sun ◽

Ying-Chao Guan ◽

...

Keyword(s):

Gene Expression ◽

Sciatic Nerve ◽

Gene Expression Profiling ◽

Differential Gene Expression ◽

Expression Profiling ◽

Diabetic Mice ◽

Differential Gene ◽

Type 2 Diabetic

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IFN Regulatory Factors 4 and 8 Expression in the NOD Mouse

Clinical and Developmental Immunology ◽

10.1155/2011/374859 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Gilles Besin ◽

Simon Gaudreau ◽

Émilie Dumont-Blanchette ◽

Michael Ménard ◽

Chantal Guindi ◽

...

Keyword(s):

Gene Expression ◽

Bone Marrow ◽

Type 1 Diabetes ◽

Nod Mice ◽

Nod Mouse ◽

Dc Functions ◽

Gm Csf ◽

Diabetes Progression ◽

Islet Inflammation

Dendritic cells (DCs) contribute to islet inflammation and its progression to diabetes in NOD mouse model and human. DCs play a crucial role in the presentation of autoantigen and activation of diabetogenic T cells, and IRF4 and IRF8 are crucial genes involved in the development of DCs. We have therefore investigated the expression of these genes in splenic DCs during diabetes progression in NOD mice. We found that IRF4 expression was upregulated in splenocytes and in splenic CD11c+DCs of NOD mice as compared to BALB/c mice. In contrast, IRF8 gene expression was higher in splenocytes of NOD mice whereas its expression was similar in splenic CD11c+DCs of NOD and BALB/c mice. Importantly, levels of IRF4 and IRF8 expression were lower in tolerogenic bone marrow derived DCs (BMDCs) generated with GM-CSF as compared to immunogenic BMDCs generated with GM-CSF and IL-4. Analysis of splenic DCs subsets indicated that high expression of IRF4 was associated with increased levels of CD4+CD8α−IRF4+CD11c+DCs but not CD4−CD8α+IRF8+CD11c+DCs in NOD mice. Our results showed that IRF4 expression was up-regulated in NOD mice and correlated with the increased levels of CD4+CD8α−DCs, suggesting that IRF4 may be involved in abnormal DC functions in type 1 diabetes in NOD mice.

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Effect of Myd88 deficiency on gene expression profiling in salivary glands of female non-obese diabetic (NOD) mice

Journal of Oral Biosciences ◽

10.1016/j.job.2021.04.003 ◽

2021 ◽

Author(s):

Taiki Mori ◽

Hideo Kataoka ◽

Takeshi Into

Keyword(s):

Gene Expression ◽

Gene Expression Profiling ◽

Salivary Glands ◽

Expression Profiling ◽

Nod Mice

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Gene Expression Analysis of the Pre-Diabetic Pancreas to Identify Pathogenic Mechanisms and Biomarkers of Type 1 Diabetes

Frontiers in Endocrinology ◽

10.3389/fendo.2020.609271 ◽

2020 ◽

Vol 11 ◽

Author(s):

Linda Yip ◽

Rebecca Fuhlbrigge ◽

Reem Alkhataybeh ◽

C. Garrison Fathman

Keyword(s):

Gene Expression ◽

Type 1 Diabetes ◽

Disease Progression ◽

Expression Analysis ◽

Peripheral Blood ◽

Gene Expression Analysis ◽

Nod Mice ◽

Human Pancreas ◽

Blood Samples

Type 1 Diabetes (T1D) occurs as a result of the autoimmune destruction of pancreatic β-cells by self-reactive T cells. The etiology of this disease is complex and difficult to study due to a lack of disease-relevant tissues from pre-diabetic individuals. In this study, we performed gene expression analysis on human pancreas tissues obtained from the Network of Pancreatic Organ Donors with Diabetes (nPOD), and showed that 155 genes were differentially expressed by ≥2-fold in the pancreata of autoantibody-positive (AA+) at-risk individuals compared to healthy controls. Only 48 of these genes remained changed by ≥2-fold in the pancreata of established T1D patients. Pathway analysis of these genes showed a significant association with various immune pathways. We were able to validate the differential expression of eight disease-relevant genes by QPCR analysis: A significant upregulation of CADM2, and downregulation of TRPM5, CRH, PDK4, ANGPL4, CLEC4D, RSG16, and FCGR2B was confirmed in the pancreata of AA+ individuals versus controls. Studies have already implicated FCGR2B in the pathogenesis of disease in non-obese diabetic (NOD) mice. Here we showed that CADM2, TRPM5, PDK4, and ANGPL4 were similarly changed in the pancreata of pre-diabetic 12-week-old NOD mice compared to NOD.B10 controls, suggesting a possible role for these genes in the pathogenesis of both T1D and NOD disease. The loss of the leukocyte-specific gene, FCGR2B, in the pancreata of AA+ individuals, is particularly interesting, as it may serve as a potential whole blood biomarker of disease progression. To test this, we quantified FCGR2B expression in peripheral blood samples of T1D patients, and AA+ and AA- first-degree relatives of T1D patients enrolled in the TrialNet Pathway to Prevention study. We showed that FCGR2B was significantly reduced in the peripheral blood of AA+ individuals compared to AA- controls. Together, these findings demonstrate that gene expression analysis of pancreatic tissue and peripheral blood samples can be used to identify disease-relevant genes and pathways and potential biomarkers of disease progression in T1D.

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