NF-κB activity in transgenic mice: developmental regulation and tissue specificity

Abstract

The transcription factor family NF-κB/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-κB/Rel family members and the Drosophila melanogaster protein DORSAL, which is activated early during embryogenesis, we were interested in determining the pattern of NF-κB activity during mouse development. Two lacZ reporter constructs, each driven by promoter elements that are dependent on the presence of nuclear NF-κB/Rel activity, were used to produce transgenic mice. The analysis of these mice did not identify nuclear NF-κB/Rel activity in early development prior to implantation or during the gastrulation processes. Earliest expression of the lacZ transgene was detected on day E12.5. Before birth lacZ expression was seen in discrete regions of the rhombencephalon of the developing brain, in the spinal medulla, in some of the blood vessels and in the thymus. After birth, the NF-κB/Rel activity in the thymus remained but nuclear activity was also found in the bone marrow, in the spleen and in the capsule of the lymph nodes. In the central nervous system, drastic changes in NF-κB/Rel activity could be observed in the first 3 weeks after birth, when the cortex and the cerebellum reach functional and morphological maturity. Considering the results of the p50, p65, relB and c-rel knock-out mice and our present findings, we believe that the NF-κB/Rel proteins known so far are probably not implicated in processes of early development and differentiation of the different tissues, but rather in maintaining their function once matured.