Title: P4‐121: Analysis of insulin‐degrading enzyme (IDE) expression and function in zebrafish embryos
Abstract: The insulin degrading enzyme (IDE) has a key role in Alzheimer's disease (AD) through its degradation of Amyloid beta peptide (Ab). Interest is growing in using zebrafish as an in vivo model to investigate the function of AD-related genes. The zebrafish IDE sequence shares 89% amino acid residue identity with human IDE and so may possess similar activity. We examined the expression pattern of IDE during zebrafish embryogenesis by in-situ hybridization. We also performed a knockdown study to investigate the IDE function in zebrafish embryos using translation-blocking antisense morpholino. Strong expression of IDE gene in the brain region was observed in zebrafish embryos. Reduction of IDE expression generated phenotypic changes characterized by severe hydrocephalus and cardiac edema and/or a curved trunk. Development of the nervous system appeared to be disturbed as shown by deficits in touch-elicited reflexes. The severe phenotype associated with loss of IDE function in zebrafish indicates that this protein plays an essential role in zebrafish development. Our results provide insights into the function of IDE during zebrafish embryogenesis that have implications for the potential of zebrafish as an AD model.