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Expression of genetically determined diabetes and insulitis in the nonobese diabetic (NOD) mouse at the level of bone marrow-derived cells. Transfer of diabetes and insulitis to nondiabetic (NOD X B10) F1 mice with bone marrow cells from NOD mice

Journal Article · · J. Exp. Med.; (United States)
; ; ; ;
The development of autoimmune diabetes in the nonobese diabetic (NOD) mouse is controlled by at least three recessive loci, including one linked to the MHC. To determine whether any of these genetic loci exert their effects via the immune system, radiation bone marrow chimeras were constructed in which (NOD X B10)F1-irradiated recipients were reconstituted with NOD bone marrow cells. Unmanipulated (NOD X B10)F1 mice, or irradiated F1 mice reconstituted with F1 or B10 bone marrow, did not display insulitis or diabetes. In contrast, insulitis was observed in a majority of the NOD----F1 chimeras and diabetes developed in 21% of the mice. These data demonstrate that expression of the diabetic phenotype in the NOD mouse is dependent on NOD-derived hematopoietic stem cells. Diabetogenic genes in the NOD mouse do not appear to function at the level of the insulin-producing beta cells since NOD----F1 chimeras not only developed insulitis and diabetes but also rejected beta cells within pancreas transplants from newborn B10 mice. These data suggest that the beta cells of the NOD mouse do not express a unique antigenic determinant that is the target of the autoimmune response.
Research Organization:
Merck Sharp and Dohme Research Laboratories, Rahway, NJ (USA)
OSTI ID:
6840215
Journal Information:
J. Exp. Med.; (United States), Journal Name: J. Exp. Med.; (United States) Vol. 167:6; ISSN JEMEA
Country of Publication:
United States
Language:
English

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Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BODY
BONE MARROW CELLS
CHIMERAS
CONNECTIVE TISSUE CELLS
DIABETES MELLITUS
DIGESTIVE SYSTEM
DISEASES
ENDOCRINE DISEASES
ENDOCRINE GLANDS
GLANDS
IMMUNE REACTIONS
MAMMALS
METABOLIC DISEASES
MICE
MOSAICISM
ORGANS
PANCREAS
PATHOGENESIS
PHENOTYPE
RADIATION CHIMERAS
RETICULOENDOTHELIAL SYSTEM
RODENTS
SOMATIC CELLS
STEM CELLS
TISSUES
TRANSPLANTS
VERTEBRATES