Functional expression of human type I interferon receptors in the mouse liver.
We expressed human type I interferon (IFN) receptors (IFNAR) in mice and investigated their signaling. Using a hydrodynamics-based delivery method, vectors containing the genes for IFNAR1 and IFNAR2 were transferred into mice. Six hours after gene-transfer, mice were intravenously injected with human IFN-alpha at 10,000 IU. IFNAR1 and IFNAR2 were both expressed in the liver, but not spleen or lung. The receptors were coexpressed in single liver cells. One hour after IFN-alpha injection, the phosphorylation status of signal transducer and activator of transcription factor 1 (STAT1), a key molecule of IFN signaling, was determined. Phosphotyrosine-STAT1 (p-STAT1), localized to the nucleus of IFNAR-expressing cells, was increased in the livers of IFNAR gene-transferred mice but not in control vector-transferred animals. In conclusion, functional human IFNAR can be delivered to the mouse liver, resulting in an increase in p-STAT1 levels following human IFN-alpha stimulation.
Tochizawa
Shiro
S
Research Institute of Pharmacological and Therapeutical Development, Otsuka Pharmaceutical Co., Ltd., Tokushima 771-0192, Japan. s_tochizawa@research.otsuka.co.jp
Muraguchi
Masahiro
M
Ohmoto
Yasukazu
Y
Oga
Keiko
K
Mori
Toyoki
T
D000818:Animals; D006801:Humans; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000378:metabolism*; D016898:Interferon-alpha / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008813:Mice, Inbred ICR; D010766:Phosphorylation; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000096:biosynthesis*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015854:Up-Regulation
C507964:IFNAR1 protein, human; C508033:IFNAR2 protein, human; C508032:Ifnar1 protein, mouse; C508034:Ifnar2 protein, mouse; D007370:Interferon Type I; D016898:Interferon-alpha; D008565:Membrane Proteins; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D053633:Receptor, Interferon alpha-beta