title: Expression of a novel murine type I IFN in the pancreatic islets induces diabetes in mice.
abstract: 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.
authors.affiliation: Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
authors.forename: Galya
authors.initials: G
authors.lastname: Vassileva
authors.forename: Shu-Cheng
authors.initials: SC
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.forename: Susan
authors.initials: S
authors.lastname: Abbondanzo
authors.forename: Kristian
authors.initials: K
authors.lastname: Jensen
authors.forename: Daniel
authors.initials: D
authors.lastname: Gorman
authors.forename: Bahige M
authors.initials: BM
authors.lastname: Baroudy
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Nicholas
authors.initials: N
authors.lastname: Murgolo
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Lira
mesh_terms: 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
chemical_list: D007370:Interferon Type I; D012330:RNA, Double-Stranded; C439669:interferon kappa; D007371:Interferon-gamma