# Targeted disruption of the aralkylamine N-acetyltransferase gene in a seasonal mammal, Mesocricetus auratus

## TL;DR

This study shows that melatonin, produced by AANAT, is crucial for seasonal survival in Syrian hamsters, affecting body temperature and hibernation.

## Contribution

The study genetically disrupts AANAT in a seasonal mammal to reveal melatonin's role in photoperiodic adaptation and thermoregulation.

## Key findings

- Mutants showed accelerated entrainment to light–dark cycles but failed to maintain normal hibernation.
- Mutants exhibited decreased body temperature and lipid droplet volume in brown adipose tissue after cold exposure.
- Defective photoperiodic responsiveness in mutants disrupted thermoregulation and hibernation cycles.

## Abstract

A definitive understanding of intrinsic functions of endogenous melatonin may require genetic manipulation or modification of its synthesizing enzymes. Here, we established Syrian hamsters, a seasonal mammal, carrying loss of function of aralkylamine N-acetyltransferase (AANAT), a rate-limiting enzyme in melatonin biosynthesis. Mutants showed a normal circadian period but an accelerated entrainment to rescheduled light–dark cycles. We next focused on the role of melatonin in autumn/winter anticipation, given the strict increase in levels during short days. On exposure to cold after habituation to short days, all controls maintained normal core body temperature (Tb), whereas many mutants showed a decrease in Tb. Food shortage after this cold exposure induced hibernation in all controls and mutants; however, all mutants failed to continue a normal hibernation cycle, probably due to impaired Tb elevation during arousal from deep hibernation. These failures were accompanied by a decreased volume of lipid droplets in the interscapular brown adipose tissue (iBAT). Histological analyses of the pars tuberalis suggested a defect in photoperiodic responsiveness in mutants. Taken together, these findings demonstrate that defective photoperiodic responsiveness caused delayed remodeling of the iBAT in mutants and that sudden exposure to autumn/winter conditions caused severe defects in Tb homeostasis and interbout arousal, in both of which iBAT-mediated nonshivering thermogenesis plays a major role. AANAT-mediated melatonin biosynthesis appears to be indispensable to the survival of wild seasonal mammals in natural settings.