NF-KAPPA-B ACTIVITY IN TRANSGENIC MICE - DEVELOPMENTAL REGULATION ANDTISSUE-SPECIFICITY

The transcription factor family NF-kappa B/Rel is responsible for the regulation of a large number of cellular genes and some viruses. Since there is a strong similarity between the NF-kappa B/Rel family member s and the Drosophila melanogaster protein DORSAL, which is activated e arly during embryogenesis, we were interested in determining the patte rn of NP-KB activity during mouse development. Two lacZ reporter const ructs, each driven by promoter elements that are dependent on the pres ence of nuclear NF-kappa B/Rel activity, were used to produce transgen ic mice. The analysis of these mice did not identify nuclear NF-kappa B/Rel activity in early development prior to implantation or during th e gastrulation processes. Earliest expression of the lacZ transgene wa s detected on day E12.5. Before birth lacZ expression was seen in disc rete regions of the rhombencephalon of the developing brain, in the sp inal medulla, in some of the blood vessels and in the thymus. After bi rth, the NF-kappa B/Rel activity in the thymus remained but nuclear ac tivity was also found in the bone marrow, in the spleen and in the cap sule of the lymph nodes. In the central nervous system, drastic change s in NF-kappa B/Rel activity could be observed in the first 3 weeks af ter birth, when the cortex and the cerebellum reach functional and mor phological maturity. Considering the results of the p50, p65, relB and c-rel knock-out mice and our present findings, we believe that the NF -kappa B/Rel proteins known so far are probably not implicated in proc esses of early development and differentiation of the different tissue s, but rather in maintaining their function once matured.