Expression of a novel murine type IIFN in the pancreatic islets induces diabetes in mice

被引:35
作者
Vassileva, G
Chen, SC
Zeng, M
Abbondanzo, S
Jensen, K
Gorman, D
Baroudy, BM
Jiang, Y
Murgolo, N
Lira, SA
机构
[1] Schering Plough Corp, Res Inst, Dept Immunol, Kenilworth, NJ 07033 USA
[2] Schering Plough Corp, Res Inst, Dept Virol, Kenilworth, NJ 07033 USA
[3] Schering Plough Corp, Res Inst, Dept Bioinformat, Kenilworth, NJ 07033 USA
[4] DNAX Res Inst Mol & Cellular Biol Inc, Palo Alto, CA 94304 USA
关键词
D O I
10.4049/jimmunol.170.11.5748
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IFN-kappa belongs to a recently identified subclass of type I IFNs. In this study, we report the cloning and preliminary characterization of the murine homologue of IFN-kappa. The gene encodes a 200-aa protein which is 38.5% homologous to human IFN-kappa. Murine IFN-kappa contains four cysteines in, analogous positions to those observed in the IFN-alpha and an additional fifth unique cysteine, C174. The murine gene is located on chromosome 4, where other type I murine IFN genes, IFN-alpha and IFN-beta, are clustered. This region is syntenic with human chromosome 9 where the gene encoding IFN-kappa and the type I IFN gene cluster are found. Mouse IFN-kappa is expressed at low levels in peritoneal macrophages and its expression is up-regulated by dsRNA and IFN-gamma. Similar to previously reported transgenic mice carrying type I and type II IFNs, transgenic mice overexpressing murine IFN-kappa in the beta cells of the pancreas develop overt diabetes with hyperglycemia. Histological characterization of pancreatic islets from these transgenic mice showed inflammatory infiltrates with corresponding destruction of beta cells.
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收藏
页码:5748 / 5755
页数:8
相关论文
共 42 条
[1]   Understanding autoimmune diabetes: insights from mouse models [J].
Adorini, L ;
Gregori, S ;
Harrison, LC .
TRENDS IN MOLECULAR MEDICINE, 2002, 8 (01) :31-38
[2]   INSULIN-DEPENDENT DIABETES-MELLITUS AS AN AUTOIMMUNE-DISEASE [J].
BACH, JF .
ENDOCRINE REVIEWS, 1994, 15 (04) :516-542
[3]   THE INTERFERONS - MECHANISMS OF ACTION AND CLINICAL-APPLICATIONS [J].
BARON, S ;
TYRING, SK ;
FLEISCHMANN, WR ;
COPPENHAVER, DH ;
NIESEL, DW ;
KLIMPEL, GR ;
STANTON, GJ ;
HUGHES, TK .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1991, 266 (10) :1375-1383
[4]   TYPE-I DIABETES - A CHRONIC AUTOIMMUNE-DISEASE OF HUMAN, MOUSE, AND RAT [J].
CASTANO, L ;
EISENBARTH, GS .
ANNUAL REVIEW OF IMMUNOLOGY, 1990, 8 :647-679
[5]   Islet allograft rejection in rats: A time course study characterizing adhesion molecule expression, MHC expression, and infiltrate immunophenotypes [J].
Coddington, DA ;
Yang, H ;
Rowden, G ;
Colp, P ;
Issekutz, TB ;
Wright, JR .
CELL TRANSPLANTATION, 1998, 7 (03) :285-297
[6]   ISOLATION AND CHARACTERIZATION OF A NOVEL INTERFERON-ALPHA-ENCODING GENE, IFN-ALPHA-11, WITHIN A MURINE IFN CLUSTER [J].
COULOMBEL, C ;
VODJDANI, G ;
DOLY, J .
GENE, 1991, 104 (02) :187-195
[7]  
FOULIS AK, 1987, LANCET, V2, P1423
[8]   AN IMPROVED METHOD FOR ISOLATION OF MOUSE PANCREATIC-ISLETS [J].
GOTOH, M ;
MAKI, T ;
KIYOIZUMI, T ;
SATOMI, S ;
MONACO, AP .
TRANSPLANTATION, 1985, 40 (04) :437-438
[9]   Local expression of transgene encoded TNF alpha in islets prevents autoimmune diabetes in nonobese diabetic (NOD) mice by preventing the development of auto-reactive islet-specific T cells [J].
Grewal, IS ;
Grewal, KD ;
Wong, FS ;
Picarella, DE ;
Janeway, CA ;
Flavell, RA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (05) :1963-1974
[10]  
Hogan B., 1986, MANIPULATING MOUSE E