Genetic approaches in mice to understand Rel/NF-κB and IκB function:: transgenics and knockouts

Rel/NF-kappa B transcription factors have been implicated in regulating a wide variety of genes important in cellular processes that include cell division, cell survival, differentiation and immunity. Here genetic models in which various Rel/NF-kappa B and I kappa B proteins have either been over-expressed or deleted in mice will be reviewed. Although expressed fairly ubiquitously, homozygous disruption of individual Rel/NF-kappa B genes generally affects the development of proper immune cell function. One exception is rela, which is essential for embryonic liver development. The disruption of genes encoding the individual subunits of the I kappa B kinase, namely IKK alpha and IKK beta, has demonstrated that IKK beta transmits the response to most common NF-kappa B inducing agents, whereas IKK alpha has an unexpected role in keratinocyte differentiation. Future studies will no doubt focus on the effect of multiple gene disruptions of members of this signaling pathway, on tissue-specific disruptions of these genes, and on the use of these mice as models for human diseases.