Funksjonelle studier av genekspresjon in vivo ved inflammatoriske sykdommer

The Blomhoff group was deeply involved in the application of the FUGE platform on transgenic mice, and the organisation of the platform. The described project builds on the expertise offered by the FUGE platform. Hallmarks of inflammation include activa tion of gene expression through the transcription factor NF-kB. We have generated transgenic reporter mice which express luciferase under the control of NF-kB, and used optical imaging to monitor transcriptional regulation through NF-kB in living mice. Th ese mice will now be crossed into genetically modified mouse models that spontaneously develop various autoimmune diseases, such as one model which is a combination of two other transgenic lines. When these are combined they start producing abnormal amoun ts of autoantibodies and develop a variety of inflammatory diseases such as arthritis, inflammatory bowels disease and encephalomyelitis. In addition, other partners have generated mouse models for arthritis based on positional cloning of the Ncf1 gene, a regulator of the ROS response and arthritis severity. The main objective or our work, during the first 18 months, is to utilize optical imaging techniques to study the role of the transcription factor NF-kB in specific events during chronic inflammation. Specific objectives of our work: 1. To test whether NF-kB, as assessed by molecular imaging, reflect the disease states in mouse models of chronic inflammation disease using luciferase 2. To cross-breed the Ncf1 mutation, the arthritis susceptible Aq gene in the Balb/c genetic background. 3. To cross-breed and validate the combined autoimmune model and the NF-kB reporter model. 4. Correlate various imaging probes in combination with imaging NF-kB activity during the onset and progression of autoimmune disease. 5. Make and validate new DNA constructs for generating new transgenic reporter mice with co-expression of reporter genes (co-expression cassettes of lucIREStk39gfp/dsred) controlled by NF-kB.