Biomaterial Database

Development of insulitis and diabetes in B cell-deficient NOD mice. 1997

M Yang, and B Charlton, and A M Gautam

Division of Molecular Medicine, John Curtin School of Medical Research, Australian National University, Canberra.

Insulin-dependent diabetes mellitus (IDDM) is believed to be an autoimmune disease that results from autoimmune destruction of the insulin-secreting beta-cells of the pancreas. In addition to a lymphocytic infiltration (insulitis) of the islets, patients with IDDM have autoantibodies directed against the components of the islet cells. Several beta-cell proteins have been identified as candidate autoantigens. The non-obese diabetic (NOD) mouse is a murine model for spontaneous IDDM. It is generally accepted that IDDM in patients and NOD mice results from the T lymphocyte-mediated destruction of beta-cells. However, the direct role of B lymphocytes in the disease process has not yet been clarified. To test directly the role of B cells in IDDM, we have generated B cell-deficient NOD mice by backcrossing the microMT-/- B cell 'knockout mice' onto the NOD background. The mice had no evidence of functional B cells as determined by flow cytometry and antibody production. We show that two out of seven of these mice developed insulitis and diabetes. These results suggest that despite an absence of B cells some NOD mice can still develop insulitis and diabetes.

UI	MeSH Term	Description	Entries
D007249	Inflammation	A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D007515	Islets of Langerhans	Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.	Islands of Langerhans,Islet Cells,Nesidioblasts,Pancreas, Endocrine,Pancreatic Islets,Cell, Islet,Cells, Islet,Endocrine Pancreas,Islet Cell,Islet, Pancreatic,Islets, Pancreatic,Langerhans Islands,Langerhans Islets,Nesidioblast,Pancreatic Islet
D003433	Crosses, Genetic	Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species.	Cross, Genetic,Genetic Cross,Genetic Crosses
D003922	Diabetes Mellitus, Type 1	A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.	Diabetes Mellitus, Brittle,Diabetes Mellitus, Insulin-Dependent,Diabetes Mellitus, Juvenile-Onset,Diabetes Mellitus, Ketosis-Prone,Diabetes Mellitus, Sudden-Onset,Diabetes, Autoimmune,IDDM,Autoimmune Diabetes,Diabetes Mellitus, Insulin-Dependent, 1,Diabetes Mellitus, Type I,Insulin-Dependent Diabetes Mellitus 1,Juvenile-Onset Diabetes,Type 1 Diabetes,Type 1 Diabetes Mellitus,Brittle Diabetes Mellitus,Diabetes Mellitus, Insulin Dependent,Diabetes Mellitus, Juvenile Onset,Diabetes Mellitus, Ketosis Prone,Diabetes Mellitus, Sudden Onset,Diabetes, Juvenile-Onset,Diabetes, Type 1,Insulin Dependent Diabetes Mellitus 1,Insulin-Dependent Diabetes Mellitus,Juvenile Onset Diabetes,Juvenile-Onset Diabetes Mellitus,Ketosis-Prone Diabetes Mellitus,Sudden-Onset Diabetes Mellitus
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001402	B-Lymphocytes	Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.	B-Cells, Lymphocyte,B-Lymphocyte,Bursa-Dependent Lymphocytes,B Cells, Lymphocyte,B Lymphocyte,B Lymphocytes,B-Cell, Lymphocyte,Bursa Dependent Lymphocytes,Bursa-Dependent Lymphocyte,Lymphocyte B-Cell,Lymphocyte B-Cells,Lymphocyte, Bursa-Dependent,Lymphocytes, Bursa-Dependent
D016688	Mice, Inbred NOD	A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.	Non-Obese Diabetic Mice,Mice, NOD,Mouse, Inbred NOD,Mouse, NOD,Non-Obese Diabetic Mouse,Nonobese Diabetic Mice,Nonobese Diabetic Mouse,Diabetic Mice, Non-Obese,Diabetic Mice, Nonobese,Diabetic Mouse, Non-Obese,Diabetic Mouse, Nonobese,Inbred NOD Mice,Inbred NOD Mouse,Mice, Non-Obese Diabetic,Mice, Nonobese Diabetic,Mouse, Non-Obese Diabetic,Mouse, Nonobese Diabetic,NOD Mice,NOD Mice, Inbred,NOD Mouse,NOD Mouse, Inbred,Non Obese Diabetic Mice,Non Obese Diabetic Mouse
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018345	Mice, Knockout	Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.	Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out