Lack of asmt1 or asmt2 Yields Different Phenotypes and Malformations in Larvae to Adult Zebrafish

Abstract

Melatonin is an indolamine derived from tryptophan, which is highly conserved throughout evolution, including in zebrafish, where it controls important cellular processes, such as circadian rhythms, oxidative stress, inflammation, and mitochondrial homeostasis. These functions of melatonin and its synthesis route are quite similar to those in humans. One of the most important enzymes in melatonin synthesis is acetylserotonin O-methyltransferase (ASMT), the rate-limiting enzyme, which catalyzes its final step. Due to genome duplication, zebrafish has two genes for this enzyme, asmt1 and asmt2. These genes show differential expression; asmt1 is primarily expressed in the retina and the pineal gland, and asmt2 is expressed in peripheral tissues, indicating different functions. Therefore, the aim of this work was to develop a mutant model for each asmt gene and to analyze their phenotypic effects in zebrafish. The results showed that the loss of 80% of the asmt2 gene affected melatonin concentration and consequently disrupted the sleep/wake rhythm in larvae, decreasing by 50% the distance traveled. In contrast, the loss of asmt1 had a greater influence on the physical condition of adults, as locomotor activity decreased by 50%, and 75% showed malformations. These data reveal distinct functional roles of melatonin depending on their site of production that may affect the development of zebrafish.