Multiple hemopoietic defects and lymphoid hyperplasia in mice lacking the transcriptional activation domain of the c-Rel protein.
The c-rel protooncogene encodes a member of the Rel/nuclear factor (NF)-kappaB 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 (Deltac-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-relDeltaCT/DeltaCT) display marked defects in proliferative and immune functions. c-relDeltaCT/DeltaCT 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-relDeltaCT/DeltaCT 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-relDeltaCT/DeltaCT mice, the lack of c-Rel activity is less efficiently compensated by other NF-kappaB proteins.
Carrasco
D
D
Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
Cheng
J
J
Lewin
A
A
Warr
G
G
Yang
H
H
Rizzo
C
C
Rosas
F
F
Snapper
C
C
Bravo
R
R
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001853:Bone Marrow / Q000473:pathology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000032:analysis; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000235:genetics*; D008089:Listeria monocytogenes / Q000472:pathogenicity; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics*; D020569:Proto-Oncogene Proteins c-rel; D019310:Pseudolymphoma / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000473:pathology; D015533:Transcriptional Activation / Q000235:genetics*; D014162:Transfection / Q000235:genetics
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel