Up Regulation of UPR-target genes in Zebrafish
Zebrafish is a good model to study diseases associated with Metabolic Syndrome not only because of high fecundity, external fertilization, and transparency but also because of high genetic homology to humans. A large number of their mutant phenotypes resemble that of humans’. In mammals, robust activation of UPR (unfolded protein response) is sufficient to cause fatty liver disease. My lab has found a zebrafish mutant that develops fatty liver disease in the embryo due to a significant up regulation of UPR. It is known that different stressors disrupt secretory pathway leading to UPR in vitro. Our project was to see if whole animals would have different responses to secretory pathway stressors. I used thapsigargin (Tg) to induce stress and see its effect on both cellular and physiological level in wild type Zebrafish. Tg disrupts Ca2+ homeostasis leading to misfolded and or unfolded proteins in the ER. I discovered that it causes both UPR and fatty liver disease in Zebrafish by characterizing Tg dose response.