Altered Somatotropic Axis in Prion knock down cells

Prion diseases or transmissible spongiform encephalopathies (TSE) are a group of fatal, neurodegenerative diseases that affect both humans (Creutzfeldt-Jakob disease) and animals including BSE (mad cow disease). The infectious nature and the transmissibility of TSE distinguishes them from other neurodegenerative diseases. The purpose of this study is to clarify the link between prions and the somatotropic axis. The results will have broad implications from defining a role for the native prion protein in healthy animals to improved diagnostics that can detect disease before neurologic signs are apparent.
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Our approach will be to first confirm altered expression of somatotropin and IGFBP2 (2 integral components of the somatotropic axis) in bovine prion knock down clones. This will help confirm that the altered expression of somatotropin and IGFBP2 is a result of decreased prion gene expression. Next, we will determine expression levels of somatotropin and IGFBP2 in prion knock down murine neuroblastoma lines. Northern blot analysis will be used to confirm that these cells have altered expression of both somatotropin and IGFBP2. Finally, we will identify potential pathways connecting the prion with the somatotropic axis using a murine signal transduction target gene array. A commercially available array was designed for this purpose and contains oligos corresponding to 96 genes associated with 18 different signal transduction pathways.