MULTIPLE HEMATOPOIETIC 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 )-kappa B family of transcriptional factors. To assess the role of the transcriptional activation domain or c-Rel in vivo, we generated mice expressing a truncated c-Rel (Delta c-Rel) that lacks the COOH-termin al 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 proliferati ve and immune functions, c-rel(Delta CT/Delta CT) animals present hist opathological 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, lympho id hyperplasia was also detected in lymph nodes, liver, lung, and stom ach. These animals present a more severe phenotype than mice lacking t he entire c-Rel protein. Thus, in c-rel(Delta CT/Delta CT) mice, the l ack of c-Rel activity is less efficiently compensated by other NF-kapp a B proteins.