Monogenic Diabetes and Integrated Stress Response Genes Display Altered Gene Expression in Type 1 Diabetes

Diabetes ◽  
2021 ◽  
pp. db210070
Author(s):  
Helmut Hiller ◽  
Dawn E. Beachy ◽  
Joeseph J. Lebowitz ◽  
Stefanie Engler ◽  
Justin R. Mason ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 1 Diabetes ◽  
Stress Response ◽  
Monogenic Diabetes ◽  
Integrated Stress Response ◽  
Altered Gene Expression ◽  
Stress Response Genes ◽  
Altered Gene

scholarly journals Monogenic Diabetes and Integrated Stress Response Genes Display Altered Gene Expression in Type 1 Diabetes

2021 ◽  
Author(s):  
Helmut Hiller ◽  
Dawn E. Beachy ◽  
Joseph J. Lebowitz ◽  
Stefanie Engler ◽  
Justin R. Mason ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Stress Response ◽  
Stress Responses ◽  
Disease Process ◽  
Monogenic Diabetes ◽  
Integrated Stress Response ◽  
Altered Expression ◽  
Increased Risk ◽  
Gene And Protein Expression

Type 1 diabetes has a multifactorial autoimmune etiology, involving environmental prompts and polygenic predisposition. We hypothesized that pancreata from individuals with and at risk for type 1 diabetes would exhibit dysregulated expression of genes associated with monogenic forms of diabetes caused by non-redundant single-gene mutations. Employing a “monogenetic transcriptomic strategy,” we measured the expression of these genes in human type 1 diabetes, autoantibody positive (autoantibody+), and control pancreas tissues using RTqPCR in accordance with the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines. Gene and protein expression were visualized <i>in situ</i> using immunofluorescence, RNAScope, and confocal microscopy. Two-dozen monogenic diabetes genes showed altered expression in human pancreata from individuals with type 1 diabetes versus unaffected controls. Six of these genes also saw dysregulation in pancreata from autoantibody+ persons at increased-risk for type 1 diabetes. As a subset of these genes are related to cellular stress responses, we measured integrated stress response (ISR) genes and identified 20 with altered expression in type 1 diabetes pancreata, including three of the four eIF2a-dependent kinases. Equally intriguing, we observed significant repression of the three arms of the ISR in autoantibody+ pancreata. Collectively, these efforts suggest monogenic diabetes and ISR genes are dysregulated early in the type 1 diabetes disease process and likely contribute to the disorder’s pathogenesis.

scholarly journals Monogenic Diabetes and Integrated Stress Response Genes Display Altered Gene Expression in Type 1 Diabetes

2021 ◽  
Author(s):  
Helmut Hiller ◽  
Dawn E. Beachy ◽  
Joseph J. Lebowitz ◽  
Stefanie Engler ◽  
Justin R. Mason ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Stress Response ◽  
Stress Responses ◽  
Disease Process ◽  
Monogenic Diabetes ◽  
Integrated Stress Response ◽  
Altered Expression ◽  
Increased Risk ◽  
Gene And Protein Expression

Type 1 diabetes has a multifactorial autoimmune etiology, involving environmental prompts and polygenic predisposition. We hypothesized that pancreata from individuals with and at risk for type 1 diabetes would exhibit dysregulated expression of genes associated with monogenic forms of diabetes caused by non-redundant single-gene mutations. Employing a “monogenetic transcriptomic strategy,” we measured the expression of these genes in human type 1 diabetes, autoantibody positive (autoantibody+), and control pancreas tissues using RTqPCR in accordance with the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines. Gene and protein expression were visualized <i>in situ</i> using immunofluorescence, RNAScope, and confocal microscopy. Two-dozen monogenic diabetes genes showed altered expression in human pancreata from individuals with type 1 diabetes versus unaffected controls. Six of these genes also saw dysregulation in pancreata from autoantibody+ persons at increased-risk for type 1 diabetes. As a subset of these genes are related to cellular stress responses, we measured integrated stress response (ISR) genes and identified 20 with altered expression in type 1 diabetes pancreata, including three of the four eIF2a-dependent kinases. Equally intriguing, we observed significant repression of the three arms of the ISR in autoantibody+ pancreata. Collectively, these efforts suggest monogenic diabetes and ISR genes are dysregulated early in the type 1 diabetes disease process and likely contribute to the disorder’s pathogenesis.

Molecular and Microscopic Analysis of Altered Gene Expression in Transgenic and Gene Targeted Mice

1996 ◽  
Vol 54 ◽  
pp. 12-13
Author(s):  
W. K. Jones ◽  
J. Robbins
Keyword(s):  
Gene Expression ◽  
Pulmonary Veins ◽  
Microscopic Analysis ◽  
Mouse Tissue ◽  
Adult Heart ◽  
Heavy Chains ◽  
Altered Gene Expression ◽  
Altered Gene ◽  
Pulmonary Myocardium

Two myosin heavy chains (MyHC) are expressed in the mammalian heart and are differentially regulated during development. In the mouse, the α-MyHC is expressed constitutively in the atrium. At birth, the β-MyHC is downregulated and replaced by the α-MyHC, which is the sole cardiac MyHC isoform in the adult heart. We have employed transgenic and gene-targeting methodologies to study the regulation of cardiac MyHC gene expression and the functional and developmental consequences of altered α-MyHC expression in the mouse.We previously characterized an α-MyHC promoter capable of driving tissue-specific and developmentally correct expression of a CAT (chloramphenicol acetyltransferase) marker in the mouse. Tissue surveys detected a small amount of CAT activity in the lung (Fig. 1a). The results of in situ hybridization analyses indicated that the pattern of CAT transcript in the adult heart (Fig. 1b, top panel) is the same as that of α-MyHC (Fig. 1b, lower panel). The α-MyHC gene is expressed in a layer of cardiac muscle (pulmonary myocardium) associated with the pulmonary veins (Fig. 1c). These studies extend our understanding of α-MyHC expression and delimit a third cardiac compartment.

Polymorphism of the MTHFR Gene is Associated with Altered Gene Expression in Colorectal Cancer

Endoscopy ◽  
2004 ◽  
Vol 36 (05) ◽  
Author(s):  
K Collins ◽  
GA Doherty ◽  
MR Sweeney ◽  
SM Byrne ◽  
AA Aftab ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Mthfr Gene ◽  
Altered Gene Expression ◽  
Altered Gene
Sign in / Sign up

Export Citation Format

Share Document