Weih, Falk and Durham, Stephen K. and Barton, Debra S. and Sha, William C. and Baltimore, David and Bravo, Rodrigo (1997) p50–NFκB Complexes Partially Compensate for the Absence of RelB: Severely Increased Pathology in p50^(-/-)relB^(-/-) Double-knockout Mice. Journal of Experimental Medicine, 185 (7). pp. 1359-1370. ISSN 0022-1007 http://resolver.caltech.edu/CaltechAUTHORS:20120203-082031231
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RelB-deficient mice (relB^(−/−)) have a complex phenotype including multiorgan inflammation and hematopoietic abnormalities. To examine whether other NF-κB/Rel family members are required for the development of this phenotype or have a compensatory role, we have initiated a program to generate double-mutant mice that are deficient in more than one family member. Here we report the phenotypic changes in relB^(−/−) mice that also lack the p50 subunit of NFκB (p50^(−/−)). The inflammatory phenotype of p50^(−/−)relB^(−/−) double-mutant mice was markedly increased in both severity and extent of organ involvement, leading to premature death within three to four weeks after birth. Double-knockout mice also had strongly increased myeloid hyperplasia and thymic atrophy. Moreover, B cell development was impaired and, in contrast to relB^(−/−) single knockouts, B cells were absent from inflammatory infiltrates. Both p50^(−/−) and heterozygous relB^(−/+) animals are disease-free. In the absence of the p50, however, relB^(−/+) mice (p50^(−/−))relB^(−/+) had a mild inflammatory phenotype and moderate myeloid hyperplasia. Neither elevated mRNA levels of other family members, nor increased κB-binding activities of NF-κB/Rel complexes could be detected in single- or double-mutant mice compared to control animals. These results indicate that the lack of RelB is, in part, compensated by other p50-containing complexes and that the “classical” p50-RelA–NF-κB activity is not required for the development of the inflammatory phenotype.
|Additional Information:||© 1997 Rockefeller University Press. Received for publication 21 January 1997. We gratefully acknowledge Kenneth Class for flow cytometry, Michele French and Sophie Komar for excellent technical assistance, and James Loy for photoimaging. We also thank Violetta Iotsova and Jorge Caamano for valuable comments on this manuscript and all the staff in Veterinary Sciences of Bristol-Myers Squibb.|
|Official Citation:||p50–NF-κB Complexes Partially Compensate for the Absence of RelB: Severely Increased Pathology in p50−/−relB−/−Double-knockout Mice Falk Weih, Stephen K. Durham, Debra S. Barton, William C. Sha, David Baltimore, and Rodrigo Bravo 185:1359-1370. doi:10.1084/jem.185.7.1359|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Ruth Sustaita|
|Deposited On:||03 Feb 2012 16:55|
|Last Modified:||26 Dec 2012 14:47|
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