250 - Characterization of the zebrafish orthologues of human extracellular superoxide dismutase

Abstract

Extracellular superoxide dismutase (SOD3) converts extracellular superoxide (O2-) into hydrogen peroxide (H2O2): a key mediator of redox signaling. Redox signaling affects diverse biological processes such as transcription, cell-cell communication, and inflammation. With respect to characterizing the inflammatory response, the zebrafish is a well-established model organism enabling researchers to study single immune cell behavior in vivo, which has supported the development of groundbreaking results highlighting the strong association between ROS and inflammation. In order to apply the zebrafish model organism for further characterization of the impact of SOD3 on the inflammatory response, we have characterized the protein chemical properties of the zebrafish orthologues, Sod3a and Sod3b. Furthermore, we have studied their expression patterns and found that they likely complement each other as they are expressed in different tissues: sod3a is mainly expressed in tissues associated with the digestive system whereas sod3b is highly expressed in cartilage and bone, and may be associated with endochondral ossification, as sod3b seems to be co-expressed with collagen10a1a in zebrafish larvae. We are currently investigating the role of SOD3 in bone mineralization in another mammalian system. Future studies we will focus on the inflammatory response using well-established models in zebrafish. We are currently creating knockout sod3a and sod3b zebrafish lines using CRISPR/Cas9 technology. These lines will provide us with a broad range of possible ways to investigate the influence of SOD3 during an inflammatory response.