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© The Rockefeller University Press, 0022-1007/1998/4/973/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 7, April 6, 1998 973-984


Articles

Multiple Hemopoietic Defects and Lymphoid Hyperplasia in Mice Lacking the Transcriptional Activation Domain of the c-Rel Protein

Daniel Carrasco*, Janet Cheng*, Anne Lewin*, Glenn Warr{ddagger}, Hyekyung Yang{ddagger}, Cheryl Rizzo*, Fabio Rosas§, Clifford Snapper§, and Rodrigo Bravo*

From the * Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000; the {ddagger} 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)-{kappa}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 ({Delta}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{Delta}CT/{Delta}CT) display marked defects in proliferative and immune functions. c-rel{Delta}CT/{Delta}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{Delta}CT/{Delta}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{Delta}CT/{Delta}CT mice, the lack of c-Rel activity is less efficiently compensated by other NF-{kappa}B proteins.


Address correspondence to Rodrigo Bravo, Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543. Phone: 609-252-5744; Fax: 609-252-6051; E-mail: bravo#m#_rodrigo{at}msmail.bms.com

1Abbreviations used in this paper: {Delta}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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