• p65fl/fl/LysMCre Transgenic Mouse Model Shows Altered Nf-Kb Signaling In Macrophages

      Howard, Shelby; Talkad, Aditi; Oza, Eesha; Department of Biological Sciences (2016-03)
      We have produced and begun characterizing a transgenic mouse model, p65fl/fl/LysMCre, that lacks canonical nuclear factor-kappaB (NF-kB) signaling (p65) in cells of the myeloid lineage, which includes macrophages. NF-kB pathway activity is very important in normal immune function, synaptic plasticity, and memory, and aberrant NF-kB activity is associated with autoimmune disease, and importantly, cancer. Macrophages can be present in very large numbers in a variety of cancers, and can lead to tumor progression through promotion of tumor inflammation, angiogenesis, invasion, and metastasis. This animal model will allow our group to pursue experiments involved in better understanding how stromal macrophages communicate with cancer cells through the NF-kB pathway, and how loss of canonical NF-kB signaling in cells of the myeloid lineage might weaken the tumor and make it more susceptible to standard treatments. Characterization of the model thus far reveals that p65 protein is indeed absent in macrophages derived from bone marrow monocytes, and that NF-kB signaling is altered when stimulated with lipopolysaccharide. We have just begun co-culture experiments with p65 deleted macrophages and glioma cells, and anticipate altered communication when compared to culture with control macrophages. Funding Source: Cancer Center Collaboration Grant