Targeted disruption of the aralkylamine <i>N</i>-acetyltransferase gene in a seasonal mammal, <i>Mesocricetus auratus</i>

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 <i>N</i>-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 (<i>T</i> _b), whereas many mutants showed a decrease in <i>T</i> _b. 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 <i>T</i> _b 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 <i>T</i> _b 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.