The c-rel protooncogene encodes a member of the Rel/nuclear factor (NF)-κB 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 (Δc-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-relΔCT/ΔCT) display marked defects in proliferative and immune functions. c-relΔCT/ΔCT 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-relΔCT/ΔCT 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-relΔCT/ΔCT mice, the lack of c-Rel activity is less efficiently compensated by other NF-κB proteins.
Multiple Hemopoietic Defects and Lymphoid Hyperplasia in Mice Lacking the Transcriptional Activation Domain of the c-Rel Protein
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#[email protected]
1Abbreviations used in this paper: Δc-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.
Daniel Carrasco, Janet Cheng, Anne Lewin, Glenn Warr, Hyekyung Yang, Cheryl Rizzo, Fabio Rosas, Clifford Snapper, Rodrigo Bravo; Multiple Hemopoietic Defects and Lymphoid Hyperplasia in Mice Lacking the Transcriptional Activation Domain of the c-Rel Protein . J Exp Med 6 April 1998; 187 (7): 973–984. doi: https://doi.org/10.1084/jem.187.7.973
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