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B Complexes Partially Compensate for the
Absence of RelB: Severely Increased Pathology in
p50
/relB/ Double-knockout Mice
By
From the * Department of Oncology, RelB-deficient mice (relB Department of Experimental Pathology, Bristol-Myers Squibb
Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; and the § Department of
Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
/) have a complex phenotype including multiorgan inflammation
and hematopoietic abnormalities. To examine whether other NF-
B/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 NFB (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 B-binding
activities of NF-B/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-B activity is not
required for the development of the inflammatory phenotype.
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