Expression of a novel murine type I IFN in the pancreatic islets induces diabetes in mice.
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.
Vassileva
Galya
G
Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Chen
Shu-Cheng
SC
Zeng
Ming
M
Abbondanzo
Susan
S
Jensen
Kristian
K
Gorman
Daniel
D
Baroudy
Bahige M
BM
Jiang
Ying
Y
Murgolo
Nicholas
N
Lira
Sergio A
SA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis* / Q000235:genetics* / Q000302:isolation & purification; D007371:Interferon-gamma / Q000494:pharmacology; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012330:RNA, Double-Stranded / Q000494:pharmacology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D007370:Interferon Type I; D012330:RNA, Double-Stranded; C439669:interferon kappa; D007371:Interferon-gamma