title: Innate immune responses in NF-kappaB-repressing factor-deficient mice.
abstract: NF-kappaB-repressing factor (NRF) is a transcriptional silencer protein that specifically counteracts the basal activity of several NF-kappaB-dependent promoters by direct binding to specific neighboring DNA sequences. In cell culture experiments, the reduction of NRF mRNA leads to a derepression of beta interferon, interleukin-8, and inducible nitric oxide synthase transcription. The X chromosome-located single-copy NRF gene is ubiquitously expressed and encodes a protein of 690 amino acids. The N-terminal part contains a nuclear localization signal, the DNA-binding domain, and the NF-kappaB-repressing domain, while the C-terminal part is responsible for double-stranded RNA binding and nucleolar localization. To study the function of NRF in a systemic context, transgenic mice lacking the NRF gene were created. Against predictions from in vitro experiments, mice with a deletion of the NRF gene are viable and have a phenotype that is indistinguishable from wild-type mice, even after challenge with different pathogens. The data hint towards an unexpected functional redundancy of NRF.
authors.affiliation: Department of Gene Regulation and Differentiation, German Research Centre for Biotechnolofy, Braunschweig, Germany.
authors.forename: Natali
authors.initials: N
authors.lastname: Froese
authors.forename: Michael
authors.initials: M
authors.lastname: Schwarzer
authors.forename: Ina
authors.initials: I
authors.lastname: Niedick
authors.forename: Ursula
authors.initials: U
authors.lastname: Frischmann
authors.forename: Mario
authors.initials: M
authors.lastname: Köster
authors.forename: Andrea
authors.initials: A
authors.lastname: Kröger
authors.forename: Peter P
authors.initials: PP
authors.lastname: Mueller
authors.forename: Mahtab
authors.initials: M
authors.lastname: Nourbakhsh
authors.forename: Bastian
authors.initials: B
authors.lastname: Pasche
authors.forename: Jörg
authors.initials: J
authors.lastname: Reimann
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Hauser
mesh_terms: D000818:Animals; D001773:Blood Cells / Q000276:immunology; D002467:Cell Nucleus / Q000737:chemistry; D004198:Disease Susceptibility / Q000276:immunology; D005347:Fibroblasts / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D007113:Immunity, Innate / Q000235:genetics; D016899:Interferon-beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D052002:NF-kappa B p50 Subunit / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; D052002:NF-kappa B p50 Subunit; C073701:Nfkb1 protein, mouse; D016899:Interferon-beta; D052247:Nitric Oxide Synthase Type II