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Titolo:
Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes
Autore:
Kecha-Kamoun, O; Achour, I; Martens, H; Collette, J; Lefebvre, PJ; Greiner, DL; Geenen, V;
Indirizzi:
Univ Liege, Inst Pathol, CHU B23, Ctr Immunol, B-4000 Liege, Belgium Univ Liege Liege Belgium B-4000 B23, Ctr Immunol, B-4000 Liege, Belgium Univ Liege, Inst Pathol, CHU B23, Dept Med, B-4000 Liege, Belgium Univ Liege Liege Belgium B-4000 CHU B23, Dept Med, B-4000 Liege, Belgium Univ Massachusetts, Sch Med, Dept Med, Diabet Div, Worcester, MA 01605 USAUniv Massachusetts Worcester MA USA 01605 et Div, Worcester, MA 01605 USA
Titolo Testata:
DIABETES-METABOLISM RESEARCH AND REVIEWS
fascicolo: 2, volume: 17, anno: 2001,
pagine: 146 - 152
SICI:
1520-7552(200103/04)17:2<146:TEOIGI>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
GROWTH-FACTOR-II; BETA-CELL FUNCTION; MESSENGER-RNAS; DEVELOPMENTAL REGULATION; INTRATHYMIC EXPRESSION; SUSCEPTIBILITY LOCUS; TRANSCRIPTION LEVELS; TRANSGENIC MICE; NERVOUS-SYSTEM; ORAL INSULIN;
Keywords:
thymus; type 1 diabetes; insulin gene family;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Geenen, V Univ Liege, Inst Pathol, CHU B23, Ctr Immunol, 1 Sart Tilman, B-4000 Liege, Belgium Univ Liege 1 Sart Tilman Liege Belgium B-4000 00 Liege, Belgium
Citazione:
O. Kecha-Kamoun et al., "Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes", DIABET M R, 17(2), 2001, pp. 146-152

Abstract

Background Insulin and multiple other autoantigens have been implicated inthe pathogenesis of autoimmune type 1 diabetes, but the origin of immunological self-reactivity specifically oriented against insulin-secreting isletbeta -cells remains obscure. The primary objective of the present study was to investigate the hypothesis that a defect in thymic central T-cell self-tolerance of the insulin hormone family could contribute to the pathophysiology of type 1 diabetes. This hypothesis was investigated in a classic animal model of type 1 diabetes, the Bio-breeding (BB) rat. Methods The expression of the mammalian insulin-related genes (ins, Igf1 and Igf2) was analysed in the thymus of inbred Wistar Furth rats (WF), diabetes-resistant BE (BBDR) and diabetes-prone BE (BBDP) rats. Results RT-PCR analyses of total RNA from WF, BBDP and BBDR thymi revealedthat Igf1 and Ins mRNAs are present in 15/15 thymi from 2-day-old, 5-day-old and Ei-week-old WF, BBDR and BBDP rats. In contrast, a complete absence of Igf2 mRNA was observed in more than 80% of BBDP thymi. The absence of detectable Igf2 transcripts in the thymus of BBDP rats is tissue-specific, since Igf2 mRNAs were detected in all BBDP brains and livers examined. Using a specific immunoradiometric assay, the concentration of thymic IGF-2 protein was significantly lower in BBDP than in BBDR rats (p < 0.01). Conclusions The present study suggests an association between the emergence of autoimmune diabetes and a defect in Igf2 expression in the thymus of BBDP rats. This tissue-specific defect in gene expression could contribute both to the lymphopenia of these rats (by impaired T-cell development) and the absence of central T-cell self-tolerance of the insulin hormone family (by defective negative selection of self-reactive T-cells). Copyright (C) 2001 John Wiley & Sons, Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/06/20 alle ore 23:58:33