The zebrafish, Danio rerio , has become an established model of human disease, due to its high fecundity and short generation time, its optical clarity during ex utero development, and its highly conserved genomic sequence compared to humans. The thesis research presented investigates the role of Cyclin D1 in early zebrafish development, as well as the roles of Cyclin D1 and p53 in the ionizing radiation-induced DNA damage response. It was determined that the targeted downregulation of zebrafish ccndi using antisense oligonucleotides containing either Morpholino or hydroxyprolyl/phosphono peptide nucleic acid backbone chemistries produced a phenotype that was similar to the phenotype observed in the ccnd1 knockout mouse. It was also discovered that ccnd1 knockdown rendered developing zebrafish embryos more sensitive to ionizing radiation treatment, while p53 knockdown rendered these embryos more resistant. This work will help provide a better understanding of the ionizing-radiation induced DNA damage response in vivo , and possibly help discover novel agents of radiosensitization and radioprotection.
