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

## TL;DR

This study shows that knocking out asmt1 or asmt2 in zebrafish leads to different effects on melatonin levels, sleep patterns, and physical development.

## Contribution

The study reveals distinct functional roles of asmt1 and asmt2 in melatonin synthesis and zebrafish development.

## Key findings

- Loss of asmt2 reduces melatonin and disrupts sleep/wake rhythms in larvae.
- Loss of asmt1 causes malformations and reduced locomotor activity in adults.
- The two asmt genes have distinct expression and functional roles in 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.