Article (Scientific journals)
Thymic Expression of Insulin-Related Genes in an Animal Model of Autoimmune Type 1 Diabetes
Kecha-Kamoun, Ouafae; Achour, Imane; Martens, Henri et al.
2001In Diabetes/Metabolism Research and Reviews, 17 (2, Mar-Apr), p. 146-52
Peer Reviewed verified by ORBi
 

Files


Full Text
Thymic IGF genes in BB rat.pdf
Publisher postprint (334.78 kB)
Download

All documents in ORBi are protected by a user license.

Send to



Details



Abstract :
[en] BACKGROUND: Insulin and multiple other autoantigens have been implicated in the pathogenesis of autoimmune type 1 diabetes, but the origin of immunological self-reactivity specifically oriented against insulin-secreting islet beta-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 BB (BBDR) and diabetes-prone BB (BBDP) rats. RESULTS: RT-PCR analyses of total RNA from WF, BBDP and BBDR thymi revealed that Igf1 and Ins mRNAs are present in 15/15 thymi from 2-day-old, 5-day-old and 5-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).
Disciplines :
Immunology & infectious disease
Endocrinology, metabolism & nutrition
Author, co-author :
Kecha-Kamoun, Ouafae
Achour, Imane
Martens, Henri ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Embryologie
Collette, Julien ;  Centre Hospitalier Universitaire de Liège - CHU > Chimie médicale
Lefebvre, Pierre J.
Greiner, Dale L.
Geenen, Vincent ;  Université de Liège - ULiège > Centre d'immunologie
Language :
English
Title :
Thymic Expression of Insulin-Related Genes in an Animal Model of Autoimmune Type 1 Diabetes
Publication date :
2001
Journal title :
Diabetes/Metabolism Research and Reviews
ISSN :
1520-7552
eISSN :
1520-7560
Publisher :
John Wiley & Sons, Hoboken, United States - New Jersey
Volume :
17
Issue :
2, Mar-Apr
Pages :
146-52
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 21 September 2009

Statistics


Number of views
160 (9 by ULiège)
Number of downloads
346 (6 by ULiège)

Scopus citations®
 
39
Scopus citations®
without self-citations
30
OpenCitations
 
30

Bibliography


Similar publications



Contact ORBi