Genetic control of diabetes and insulitis in the nonobese diabetic mouse. Pedigree analysis of a diabetic H-2nod/b heterozygote.
The development of autoimmune type 1 diabetes mellitus in man and the nonobese diabetic (NOD) mouse is greatly influenced by a gene linked to the MHC. Although homozygosity at the NOD MHC is required for a high prevalence of disease, during backcross studies we have found a small number of diabetic H-2nod/b MHC heterozygotes. These diabetic heterozygotes could either represent a crossover event between the MHC and a putative MHC-linked diabetogenic gene or, alternatively, they could indicate that there is a dominant MHC-linked diabetic gene that has low penetrance in the heterozygous state. Pedigree analysis of a diabetic H-2nod/b MHC heterozygote favors the latter hypothesis.
Wicker
L S
LS
Department of Immunology Research, Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065.
Miller
B J
BJ
Fischer
P A
PA
Pressey
A
A
Peterson
L B
LB
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000473:pathology; D003433:Crosses, Genetic; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000473:pathology; D005260:Female; D006183:H-2 Antigens / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D007515:Islets of Langerhans / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D010375:Pedigree
D006183:H-2 Antigens