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Department of Microbiology, Bristol-Myers Squibb Pharmaceutical Research Institute,Wallingford, Connecticut 06492; and the
Department of Pathology, Uniformed Services, University of Health Sciences, Bethesda, Maryland 20814
The c-rel protooncogene encodes a member of the Rel/nuclear factor (NF)-
B family of transcriptional factors. To assess the role of the transcriptional activation domain of c-Rel in vivo, we generated mice expressing a truncated c-Rel (
c-Rel) that lacks the COOH-terminal region, but retains a functional Rel homology domain. Mice with an homozygous mutation in the c-rel region encoding the COOH terminus of c-Rel (c-rel
CT/
CT) display marked defects in proliferative and immune functions. c-rel
CT/
CT animals present histopathological alterations of hemopoietic tissues, such as an enlarged spleen due to lymphoid hyperplasia, extramedullary hematopoiesis, and bone marrow hypoplasia. In older c-rel
CT/
CT mice, lymphoid hyperplasia was also detected in lymph nodes, liver, lung, and stomach. These animals present a more severe phenotype than mice lacking the entire c-Rel protein. Thus, in c-rel
CT/
CT mice, the lack of c-Rel activity is less efficiently compensated by other NF-
B proteins.
1Abbreviations used in this paper:
c-Rel, truncated c-Rel; CAT, chloramphenicol acetyl transferase; CD, cluster of differentiation; EMSA, electrophoretic mobility shift assay; ES, embryonic stem; GC, germinal center; Gr-1, granulocyte 1; LCMV, lymphocytic choriomeningitis virus; Mac-1, macrophage 1; mCD40L, ligand for the mouse CD40; NF, nuclear factor; p, protein; p(A), polyadenylation sequence; PGK, phosphoglycerate kinase; pPNT, plasmid PGK promoter neomycin thymidine kinase; RHD, Rel homology domain; Ter, total erythroid cells. D. Carrasco's present address is Department of Pathology, Massachusetts General Hospital, Boston, MA 02114.
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