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429 results on '"Mordes, John P."'

2. Immunotherapy of the BB Rat *

Author

Mordes, John P., primary, Handler, Eugene S., additional, Burstein, Dina, additional, Greiner, Dale L., additional, and Rossini, Aldo A., additional

Published
2019
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13. Autoantigen-induced focusing of Vβ[13.sup.+] T cells precedes onset of autoimmune diabetes in the LEW.1WR1 Rat

Author

Eberwine, Ryan A., Cort, Laura, Habib, Michael, Mordes, John P., and Blankenhorn, Elizabeth P.

Subjects
T cells -- Physiological aspects, Type 1 diabetes -- Physiological aspects -- Causes of, Autoantigens -- Physiological aspects, Health
Abstract

The earliest events leading to autoimmune type 1 diabetes (T1D) are not known in any species. A T-cell receptor (TCR)-variable region, TCR-Vβ13, is required for susceptibility to autoimmune diabetes in rats, and selective depletion of Vβ[13.sup.+] T cells with an allele-specific monoclonal antibody prevents disease in multiple rat strains. To investigate the role of VI313 early in diabetes, we examined islet T-cell transcripts in susceptible (LEW.1WR1) and resistant (LEW.1W and Wistar Furth) strains induced with polyinosinic: polycytidylic acid. Vβ[13.sup.+] T cells displayed antigenic focusing in LEW.1WR1 islets 5 days postinduction and were characterized by a substantial decrease in complementarity determining region 3 diversity. This occurred prior to significant islet T-cell accumulation (day 7) or frank diabetes (days 10-14). Vβ[13.sup.+] transcripts increased in LEW.1WR1 islets during diabetes progression, but not in resistant rats. We also analyzed transcript clonality of rat TCR-Vα5, an ortholog of the dominant TCR-Vα chain found on insulin B:9-23-reactive T cells in nonobese diabetic rat islets. We observed clonal expansion of Vα[5.sup.+] transcripts in prediabetic LEW.1WR1 islets, suggesting that rat Vα5 is also an important component of islet autoantigen recognition. These data provide additional evidence that genome-encoded TCR sequences are important determinants of genetic susceptibility to T1D, Diabetes 2014;63:596-604 | DOI: 10.2337/db13-0462, Type 1A diabetes (T1D) is an autoimmune disease characterized by T cell-mediated destruction of insulin-producing pancreatic β-cells. T1D is thought to arise through the interaction of genetic and environmental factors, [...]

Published
2014
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24. Requirement of the JIP1 scaffold protein for stress-induced JNK activation

Author

Whitmarsh, Alan J., Kuan, Chia-Yi, Kennedy, Norman J., Kelkar, Nyaya, Haydar, Tarik F., Mordes, John P., Appel, Michael, Rossini, Aldo A., Jones, Stephen N., Flavell, Richard A., Rakic, Pasko, and Davis, Roger J.

Subjects
Cytochemistry -- Research, Protein kinases -- Research, Cellular control mechanisms -- Research, Neurons -- Physiological aspects, Biological sciences
Abstract

The need of the JIP1 scaffold protein for stress-induced c-Jun N-terminal kinase (JNK) activation is discussed. JIP1 is in the neurites of primary hippocampal neurons but in response to stress accumulates in the soma with activated JNK and phosphorylated c-Jun.

Published
2001

38. Genetic Variation Within the HLA-DRA1 Gene Modulates Susceptibility to Type 1 Diabetes in HLA-DR3 Homozygotes

Author

Aydemir, Ozkan, Noble, Janelle A., Bailey, Jeffrey A., Lernmark, Ake, Marsh, Patrick, Svard, Agnes Andersson, Bearoff, Frank, Blankenhorn, Elizabeth P., Mordes, John P., Persson, Martina, Larsson, Helena Elding, Forsander, Gun, Ivarsson, Sten-Anders, Ludvigsson, Johnny, Marcus, Claude, Carlsson, Annelie, Aydemir, Ozkan, Noble, Janelle A., Bailey, Jeffrey A., Lernmark, Ake, Marsh, Patrick, Svard, Agnes Andersson, Bearoff, Frank, Blankenhorn, Elizabeth P., Mordes, John P., Persson, Martina, Larsson, Helena Elding, Forsander, Gun, Ivarsson, Sten-Anders, Ludvigsson, Johnny, Marcus, Claude, and Carlsson, Annelie

Abstract

Type 1 diabetes (T1D) involves the interaction of multiple gene variants, environmental factors, and immunoregulatory dysfunction. Major T1D genetic risk loci encode HLA-DR and -DQ. Genetic heterogeneity and linkage disequilibrium in the highly polymorphic HLA region confound attempts to identify additional T1D susceptibility loci. To minimize HLA heterogeneity, T1D patients (N = 365) and control subjects (N = 668) homozygous for the HLA-DR3 high-risk haplotype were selected from multiple large T1D studies and examined to identify new T1D susceptibility loci using molecular inversion probe sequencing technology. We report that risk for T1D in HLA-DR3 homozygotes is increased significantly by a previously unreported haplotype of three single nucleotide polymorphisms (SNPs) within the first intron of HLA-DRA1. The homozygous risk haplotype has an odds ratio of 4.65 relative to the protective homozygous haplotype in our sample. Individually, these SNPs reportedly function as "expression quantitative trait loci," modulating HLA-DR and -DQ expression. From our analysis of available data, we conclude that the tri-SNP haplotype within HLA-DRA1 may modulate class II expression, suggesting that increased T1D risk could be attributable to regulated expression of class II genes. These findings could help clarify the role of HLA in T1D susceptibility and improve diabetes risk assessment, particularly in high-risk HLA-DR3 homozygous individuals., Funding Agencies|National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, National Human Genome Research Institute, National Institute of Child Health and Human Development; JDRF; American Diabetes Association [1-19-ICTS-076]; UMass Memorial Healthcare JL Stock Fund; National Institutes of Health [AI 39095]; [U01 DK062418]

Published
2019
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46. The iddm4 locus segregates with diabetes susceptibility in congenic WF .iddm4 rats

Author

Mordes, John P., Leif, Jean, Novak, Stephen, DeScipio, Cheryl, and Greiner, Dale L.

Subjects
Diabetes -- Genetic aspects -- Research, Health, Genetic aspects, Reports
Abstract

Viral antibody-free BBDR and WF rats never develop spontaneous diabetes. BBDR rats, however, develop autoimmune diabetes after perturbation of the immune system, e.g., by viral infection. We previously identified a disease-susceptibility locus in the BBDR rat, iddm4, which is associated with the development of autoimmune diabetes after treatment with polyinosinic:polycytidylic acid and an antibody that depletes ART[2.sup.+] regulatory cells. We have now developed lines of congenic WF.iddm4 rats and report that in an intercross of N5 generation WF.iddm4 rats, ~70% of animals either homozygous or heterozygous for the BBDR origin allele of iddm4 became hyperglycemic after treatment to induce diabetes. Fewer than 20% of rats expressing the WF origin allele of iddm4 became diabetic. Testing the progeny of various recombinant N5 WF.iddm4 congenic rats for susceptibility to diabetes suggests that iddm4 is centered on a small segment of chromosome 4 bounded by the proximal marker D4Rat135 and the distal marker D4Got51, an interval of, Type 1A autoimmune diabetes is heritable, but the mode of inheritance is complex and non-Mendelian (1). Intensive analysis has identified several high-risk class II major histocompatibility complex (MHC) haplotypes associated [...]

Published
2002

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