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The NFκB luciferase mouse: a new tool for real time measurement of NFκB activation in the whole animal
  1. D A Mann
  1. Liver Research Group, University of Southampton, Southampton, UK; dam2@soton.ac.uk

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Development of transgenic mice that express luciferase under the control of nuclear factor κB (NFκB) enables real time in vivo imaging of NFκB activity in intact animals

Of the many different transcription factors found in mammalian cells by far the best known among scientists and clinicians alike is nuclear factor κB (NFκB). In addition to its pivotal role as a regulator of innate and adaptive immune responses, NFκB has also been linked as a contributory factor in many human disorders.1 NFκB stimulates transcription of over 150 different genes encoding cytokines, adhesion molecules, immunoreceptors, acute phase proteins, enzymes, and regulators of the cell cycle and apoptosis.2 Transcription of these genes is stimulated in response to binding of NFκB to a specific 10 base pair DNA sequence (GGGRNNYYCC, where R corresponds to a purine, Y represents a pyrimidine, and N can be any base) located in either the enhancer or upstream promoter regions of a gene. Binding of NFκB to these sequences is tightly regulated by the inhibitory function of the IκB-α protein which forms a complex with NFκB that masks functional domains of the transcription factor required for its nuclear localisation and DNA binding activities. The mechanism by which IκB-α bound NFκB is activated is now well understood (fig 1).3 Following stimulation of the cell by an extracellular signal, such as the interaction of tumour necrosis factor α with its receptor, the recently discovered IκB kinase (IKK) complex is activated. The IKK complex then catalyses phosphorylation of IκB-α at two N terminal serine residues (ser 32 and 36) which then renders IκB-α a substrate for ubiquitination and finally …

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