Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of RelB, a member of the NF-kappa B/Rel family.
RelB, a member of the NF-kappa B/Rel family of transcription factors, has been implicated in the constitutive expression of kappa B-regulated genes in lymphoid tissues. We have generated mice carrying a germline mutation of the relB gene, resulting in the absence of RelB protein and a dramatic reduction of constitutive kappa B-binding activity in thymus and spleen. Mice homozygous for the disrupted relB locus had phenotypic abnormalities including multifocal, mixed inflammatory cell infiltration in several organs, myeloid hyperplasia, splenomegaly due to extramedullary hematopoiesis, and a reduced population of thymic dendritic cells. RelB-deficient animals also had an impaired cellular immunity, as observed in contact sensitivity experiments. Thus, RelB plays a decisive role in the hematopoietic system, and its absence cannot be functionally compensated by any other member of the NF-kappa B/Rel family.
Weih
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Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
Carrasco
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Durham
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Barton
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Rizzo
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Ryseck
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Lira
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Bravo
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D000375:Aging / Q000276:immunology*; D000818:Animals; D001755:Blastocyst / Q000502:physiology; D001853:Bone Marrow / Q000254:growth & development / Q000473:pathology / Q000502:physiology; D005091:Exons; D005260:Female; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000235:genetics*; D007111:Immunity, Cellular; D007249:Inflammation; D007438:Introns; D008099:Liver / Q000254:growth & development / Q000473:pathology / Q000502:physiology; D008168:Lung / Q000254:growth & development / Q000473:pathology / Q000502:physiology; D008198:Lymph Nodes / Q000254:growth & development / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000096:biosynthesis* / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D013154:Spleen / Q000254:growth & development / Q000473:pathology / Q000502:physiology; D013234:Stem Cells / Q000502:physiology; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D014162:Transfection
D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497594:Relb protein, mouse; D014157:Transcription Factors; D051841:Transcription Factor RelB