Related Experiment Video
Updated: Jul 9, 2026
09:52
Generation of High Quality Chromatin Immunoprecipitation DNA Template for High-throughput Sequencing (ChIP-seq)
Published on: April 19, 2013
Interactions between Idd5.1/Ctla4 and other type 1 diabetes genes
Kara Hunter1, Dan Rainbow, Vincent Plagnol
1Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.
Journal of Immunology (Baltimore, Md. : 1950)
|December 7, 2007
Summary
Genetic interactions between four type 1 diabetes (T1D) loci on mouse chromosome 1 influence T1D susceptibility. Interactions involving Ctla4 and Idd5.4 explain human CTLA4
Area of Science:
- Immunogenetics
- Type 1 Diabetes Research
- Mouse Models of Autoimmunity
Background:
- Type 1 diabetes (T1D) susceptibility in NOD mice is influenced by multiple genetic loci on chromosome 1.
- Idd5.1 is associated with Ctla4, affecting T cell signaling, and Idd5.2 with Nramp1, involved in host defense and antigen presentation.
- Previous studies identified Idd5.1 and Idd5.2, but additional loci and their interactions were unexplored.
Purpose of the Study:
- To identify and characterize additional T1D susceptibility loci on mouse chromosome 1.
- To investigate genetic interactions among known and newly identified T1D loci.
- To elucidate the role of these interactions in explaining the association of human CTLA4 with T1D.
Main Methods:
- Fine-mapping of chromosome 1 to define the locations of Idd5.3 and Idd5.4.
- Analysis of genetic interactions between Idd5.1, Idd5.2, Idd5.3, and Idd5.4 in NOD mice.
- Evaluation of the impact of specific alleles at these loci on T1D incidence.
Main Results:
- Two novel T1D susceptibility loci, Idd5.3 and Idd5.4, were mapped to specific regions on chromosome 1.
- Strong evidence for epistatic interactions between the four identified T1D loci was observed.
- The protective effect of the Ctla4 resistance allele was significantly modulated by alleles at Idd5.4, Idd5.2, and Idd5.3.
Conclusions:
- Genetic background critically influences the impact of Ctla4 alleles on T1D susceptibility.
- Interactions between Idd5.1, Idd5.2, Idd5.3, and Idd5.4 provide a genetic explanation for the variable association of human CTLA4 with T1D.
- These findings highlight the complexity of T1D pathogenesis and the importance of gene-gene interactions.
Related Concept Videos
01:12Type I Diabetes I: Introduction
Type 1 diabetes mellitus is a chronic metabolic disorder characterized by an absolute deficiency of insulin resulting from the autoimmune destruction of pancreatic β-cells. Although it can occur at any age, it is most commonly diagnosed in childhood, adolescence, or early adulthood. The loss of insulin production impairs cellular glucose uptake, resulting in persistent hyperglycemia and necessitating lifelong insulin therapy.Autoimmune Destruction of β-CellsThe hallmark of type 1 diabetes is an...
01:26Type I Diabetes II: Pathophysiology
Type 1 diabetes mellitus arises from an immune-mediated destruction of pancreatic β-cells, resulting in an absolute deficiency of insulin. This process develops in genetically susceptible individuals when autoimmunity, environmental exposures, and immunologic dysregulation converge to trigger a targeted attack on the insulin-producing cells of the pancreas. The β-cells are located within the islets of Langerhans and are essential for regulating blood glucose by facilitating cellular uptake of...
01:26Type II Diabetes I: Introduction
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, in which target tissues such as the liver, muscle, and adipose tissue respond poorly to insulin. It is also associated with inadequate compensatory insulin secretion, where pancreatic β-cells fail to produce sufficient insulin. Together, these abnormalities lead to persistent hyperglycemia.EtiologyT2DM develops through a complex interaction of genetic predisposition and environmental or...
01:22Diabetes Mellitus: Overview and Type I Subtype
Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
01:24Type II Diabetes II: Pathophysiology
PathophysiologyType 2 diabetes mellitus (T2DM ) is a chronic metabolic disorder characterized by insulin resistance and progressive pancreatic β-cell dysfunction, leading to impaired glucose homeostasis. It results from interactions among genetic predisposition, environmental factors, and metabolic stressors, such as overnutrition and a sedentary lifestyle.Insulin Resistance and Glucose DysregulationEarly T2DM involves insulin resistance in skeletal muscle, adipose tissue, and the liver.
01:19Type I Diabetes III: Clinical Manifestations
Type 1 diabetes mellitus typically presents with rapid-onset symptoms due to the body’s inability to utilize glucose in the absence of insulin. Since insulin is required for glucose uptake into cells, its deficiency leads to hyperglycemia and cellular energy deprivation, resulting in characteristic clinical features.Polyuria and PolydipsiaOne of the earliest, most prominent symptoms is polyuria (excessive urination). When blood glucose concentrations rise above the renal threshold, the kidneys...