Innate immune responses in NF-kappaB-repressing factor-deficient mice.
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.
Froese
Natali
N
Department of Gene Regulation and Differentiation, German Research Centre for Biotechnolofy, Braunschweig, Germany.
Schwarzer
Michael
M
Niedick
Ina
I
Frischmann
Ursula
U
Köster
Mario
M
Kröger
Andrea
A
Mueller
Peter P
PP
Nourbakhsh
Mahtab
M
Pasche
Bastian
B
Reimann
Jörg
J
Staeheli
Peter
P
Hauser
Hansjörg
H
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*
D008070:Lipopolysaccharides; D052002:NF-kappa B p50 Subunit; C073701:Nfkb1 protein, mouse; D016899:Interferon-beta; D052247:Nitric Oxide Synthase Type II