Development of Integrated Transparent Transgenic Zebrafish Modeling System for Experimental Cardio-oncology Therapeutics

The zebrafish model has provided an excellent platform to study the genetic and molecular approach of basic and translational cardiac research. Zebrafish heart cells are similar to human heart cells at the molecular level and determine the function of genes that control cardiac function and dysfunction. In zebrafish, myl7 is myosin light chain-7 gene and identified as a regulatory gene of heart orthologs to human MYL7. In vertebrates, including zebrafish, murine and human systems, the in-vivo spatial resolution is limited due to the normal opacification of skin and subdermal structures. For in-vivo imaging the skin transparency is primary requirement and to maintain the transparency, blocking the pigmentation needs to maintain. Chemical inhibition treatment is temporary and possible till the organism treated with the chemical inhibitor agent. Zebrafish casper mutant maintain transparency throughout the life and serve as ideal combination of sensitivity and resolution for in-vivo stem cell analyses and in-vivo imaging. To maintain the skin transparency, in this study, we have developed transparent transgenic zebrafish model and established of time lapse in-vivo confocal microscopy to study of cellular phenotype/pathologies of the cardiomyocytes to quantify changes in cardiomyocyte morphology and function overtime by comparing control and cardiac injury by generating casper/ myl7:RFP; annexin-5:YFP transgenic zebrafish. In the field of cardio-oncology, we are developing in-vivo transparent transgenic cellular phenotype model of zebrafish to study of the cell death process (Annexin5) and Inflammatory activity (NFkB) in the microglia, and the resident macrophage of the brain and cardiomyocytes) homozygous casper/ myl7:RFP; annexin-5:YFP/NF-kB:GFP/mpeg1:mcherryFP transgenic strain zebrafish. By using this novel model our lab establishing the role of NFkB and microglia function under normal healthy status and in glioblastomas Our strategist approach to yield crucial new insights into in-vivo cardiomyocyte imaging by confocal microscopy to observe and track the cell death pattern and cardio inflammatory pathways in cardiomyocyte and develop novel therapeutic approaches to treat cardio inflammatory pathology and glioblastoma