Therapeutic XMU-MP-1 application in desma mutant zebrafish model

In this thesis, the application of XMU-MP-1 drug candidate molecule which is a MST1 / 2 kinase inhibitor and selectively inhibits the Hippo pathway was performed by mixing the drug with zebrafish embryo egg water or adult fish by intramuscular injection. The main aim of this study is creating an algorithm and technical infrastructure related to toxicity and drug applications assays which are required for screening drug candidate molecules in zebrafish embryos and adult fish. Along with developing the drug application algorithm and standardization of the technical infrastructure, we applied XMU-MP-1 to desma mutant kg155 (-/-) zebrafish which were assumed to have defects in mechanotransduction signaling and we assessed the therapeutic efficacy of the molecule by targeting the expression level of ankrd1a. As a result, the algorithm and related technical infrastructure which are required for application of drug candidate molecules to embryos or adult fish have been successfully procured. Moreover, when control and experimental groups (desma mutant kg155 (-/-) embryos and adults) compared, ankrd1a expression level was not changed. This thesis was funded by the HU BAP Coordination Unit (Project No: 17472). The project for generating of desma mutant kg155 (-/-) zebrafishes which were used in toxicity and infrastructure of zebrafish laboratory in the scoop of this study was granted by TUBİTAK (214S174 project number). The required ethical approval for this thesis was obtained from HU Animal Experiments Local Ethics Committee with decision number 2018 / 33-10.