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Molecular and Cellular Biology, January 2006, p. 293-302, Vol. 26, No. 1
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.1.293-302.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Innate Immune Responses in NF-{kappa}B-Repressing Factor-Deficient Mice

Natali Froese,1 Michael Schwarzer,1,{dagger} Ina Niedick,1 Ursula Frischmann,2 Mario Köster,1 Andrea Kröger,1 Peter P. Mueller,1 Mahtab Nourbakhsh,1,{ddagger} Bastian Pasche,3 Jörg Reimann,4 Peter Staeheli,5 and Hansjörg Hauser1*

Department of Gene Regulation and Differentiation,1 Department of Experimental Immunology,2 Department of Infection Genetics, German Research Centre for Biotechnology, Braunschweig, Germany,3 Department of Internal Medicine I, University of Ulm, Ulm, Germany,4 Department of Virology, University of Freiburg, Freiburg, Germany5

Received 27 June 2005/ Returned for modification 7 August 2005/ Accepted 3 September 2005

NF-{kappa}B-repressing factor (NRF) is a transcriptional silencer protein that specifically counteracts the basal activity of several NF-{kappa}B-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-{kappa}B-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.


* Corresponding author. Mailing address: GBF, Dept. of Gene Regulation and Differentiation, Mascheroder Weg 1, D-38124 Braunschweig, Germany. Phone: 49 531 6181 250. Fax: 49 531 6181 262. E-mail: HHA{at}GBF.DE.

{dagger} Present address: Tulane University School of Medicine, Department of Medicine, New Orleans, La.

{ddagger} Present address: Institute of Pharmacology, Medical University of Hannover, Hannover, Germany.


Molecular and Cellular Biology, January 2006, p. 293-302, Vol. 26, No. 1
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.1.293-302.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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