Association of Susceptibility to Spontaneous Diabetes in Rat With Genes of Major Histocompatibility Complex

Diabetes ◽  
1988 ◽  
Vol 37 (10) ◽  
pp. 1438-1443 ◽  
Author(s):  
E. Colle ◽  
S. J. Ono ◽  
A. Fuks ◽  
R. D. Guttmann ◽  
T. A. Seemayer
Keyword(s):  
Major Histocompatibility Complex ◽  
Spontaneous Diabetes ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

Association of susceptibility to spontaneous diabetes in rat with genes of major histocompatibility complex

Diabetes ◽  
1988 ◽  
Vol 37 (10) ◽  
pp. 1438-1443 ◽  
Author(s):  
E. Colle ◽  
S. J. Ono ◽  
A. Fuks ◽  
R. D. Guttmann ◽  
T. A. Seemayer
Keyword(s):  
Major Histocompatibility Complex ◽  
Spontaneous Diabetes ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

scholarly journals Spontaneous diabetes mellitus syndrome in the rat. I. Association with the major histocompatibility complex.

1981 ◽  
Vol 154 (4) ◽  
pp. 1237-1242 ◽  
Author(s):  
E Colle ◽  
R D Guttmann ◽  
T Seemayer
Keyword(s):  
Diabetes Mellitus ◽  
Major Histocompatibility Complex ◽  
Spontaneous Diabetes ◽  
Breeding Pair ◽  
Insulin Content ◽  
Major Histocompatibility ◽  
F1 Hybrid ◽  
Histocompatibility Complex ◽  
Mhc Haplotype ◽  
Inbred Rat

A syndrome of spontaneous diabetes mellitus has been previously described in a partially inbred rat strain called BB Wistar. We have determined whether there is major histocompatibility complex (MHC) linkage as well as other predisposing haplotype-associated factors of development. BB rats are RT1 (MHC) genotype u/u. Using BB x Lewis F1 hybrid matings, an F2 study analyzed 128 rats from 8 primary and 3 additional litters from a breeding pair producing a diabetic offspring. 4 of 128 F2 rats, all from the 48 progeny of same breeding pair, became clinically diabetic. The four diabetics were all genotype u/u (P = 0.03). In the primary F2 litters, haplotype distribution was not different from the 1:2:1 expected ratio. However, in the four litters from the from the F1 breeding pair producing diabetics, there was an increased number of u/u animals. Two-way analysis of variance revealed significant differences in pancreatic insulin content between litters (diabetics excluded), P less than 0.001, and between haplotypes P less than 0.007 with heterozygous u/u less than 1/1 progeny. The glucagon content showed no significant differences. These data demonstrate (a) MHC linkage with spontaneous diabetes in this rat model; (b) penetrance similar to the human disease; and (c) a possible association of MHC haplotype with pancreatic inflammation as well as insulin content in nondiabetic F2 siblings.

scholarly journals Autoimmune syndromes in major histocompatibility complex (MHC) congenic strains of nonobese diabetic (NOD) mice. The NOD MHC is dominant for insulitis and cyclophosphamide-induced diabetes.

1992 ◽  
Vol 176 (1) ◽  
pp. 67-77 ◽  
Author(s):  
L S Wicker ◽  
M C Appel ◽  
F Dotta ◽  
A Pressey ◽  
B J Miller ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Autoimmune Diabetes ◽  
Spontaneous Diabetes ◽  
Nod Mice ◽  
Nod Mouse ◽  
Major Histocompatibility ◽  
Nonobese Diabetic ◽  
Histocompatibility Complex ◽  
Genes Encoding ◽  
Lymphocytic Infiltrates

The development of autoimmune diabetes in the nonobese diabetic (NOD) mouse is controlled by multiple genes. At least one diabetogenic gene is linked to the major histocompatibility complex (MHC) of the NOD and is most likely represented by the two genes encoding the alpha and beta chains of the unique NOD class II molecule. Three other diabetogenic loci have recently been identified in the NOD mouse and are located on chromosomes 1, 3, and 11. In addition to the autoimmune diabetes which is caused by destruction of the insulin-producing beta cells in the pancreas, other manifestations of autoimmunity are seen in the NOD mouse. These include mononuclear cell inflammation of the submandibular and lacrimal glands, as well as the presence of circulating autoantibodies. To determine the effect of the non-MHC diabetogenic genes on the development of autoimmunity, we constructed the NOD.B10-H-2b (NOD.H-2b) strain, which possesses the non-MHC diabetogenic genes from the NOD mouse, but derives its MHC from the C57BL/10 (B10) strain. The NOD.H-2b strain does not develop insulitis, cyclophosphamide-induced diabetes, or spontaneous diabetes. It does, however, develop extensive lymphocytic infiltrates in the pancreas and the submandibular glands that are primarily composed of Thy 1.2+ T cells and B220+ B cells. In addition, autoantibodies are present in NOD.H-2b mice which recognize the "polar antigen" on the insulin-secreting rat tumor line RINm38. These observations demonstrate that the non-MHC genes in the NOD strain, in the absence of the NOD MHC, significantly contribute to the development of autoimmunity. The contribution of a single dose of the NOD MHC to autoimmunity was assessed with a (NOD x NOD.H-2b)F1 cross. Although only approximately 3% of F1 females developed spontaneous diabetes, approximately 50% of both female and male F1 mice developed insulitis, and 25% of females and 17% of males became diabetic after treatment with cyclophosphamide. These data demonstrate that the MHC-linked diabetogenic genes of the NOD mouse are dominant with decreasing levels of penetrance for the following phenotypes: insulitis greater than cyclophosphamide-induced diabetes greater than spontaneous diabetes.

Relationship of Major Histocompatibility Complex Class II Genes to Inhibitor Antibody Formation in Hemophilia A

1990 ◽  
Vol 64 (04) ◽  
pp. 564-568 ◽  
Author(s):  
Lloyd E Lippert ◽  
Lyman Mc A Fisher ◽  
Lawrence B Schook
Keyword(s):  
Major Histocompatibility Complex ◽  
Factor Viii ◽  
Antibody Formation ◽  
Rflp Analysis ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Odds Ratios ◽  
Inhibitory Antibody ◽  
Histocompatibility Complex ◽  
Hla Dr

SummaryApproximately 14% of transfused hemophiliacs develop an anti-factor VIII inhibitory antibody which specifically neutralizes factor VIII procoagulant activity. In this study an association of the major histocompatibility complex (MHC) with inhibitor antibody formation was evaluated by restriction fragment length polymorphism (RFLP) analysis using BamHI, EcoRI, HindII, PstI, PvuII and TaqI digested genomic DNA probed with DP beta, DQ alpha, DQ beta and DR beta class II MHC gene probes. The RFLP patterns for 16 non-inhibitor and 11 inhibitor hemophiliac patients were analyzed. These 24 enzyme:probe combinations generated 231 fragments. Fifteen (15) fragments associated with the inhibitor phenotype; odds ratios ranged from 5.1 to 45 and lower bounds of 95% confidence intervals were > 1.000 for all 15 fragments. Five (5) fragments associated with non-inhibitors, with odds ratios ranging from 6.4 to 51.7. This report establishes a MHC related genetic basis for the inhibitor phenotype. No statistically significant differences in the distribution of serologically defined HLA-DR phenotypes were observed between the inhibitor and non-inhibitor groups.

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