title: Unique food-entrained circadian rhythm in cysteine414-alanine mutant mCRY1 transgenic mice.
abstract: Food availability is a potent environmental cue that directs circadian locomotor activity in rodents. Daily scheduled restricted feeding (RF), in which the food available time is restricted for several hours each day, elicits anticipatory activity. This food-anticipatory activity (FAA) is controlled by a food-entrainable oscillator (FEO) that is distinct from the suprachiasmatic nucleus (SCN), the master pacemaker in mammals. In an earlier report, we described generation of transgenic (Tg) mice ubiquitously overexpressing cysteine414-alanine mutant mCRY1. The Tg mice displayed long locomotor free-running periods (approximately 28 h) with rhythm splitting. Furthermore, their locomotor activity immediately re-adjusted to the advance of light-dark cycles (LD), suggesting some disorder in the coupling of SCN neurons. The present study examined the restricted feeding cycle (RF)-induced entrainment of locomotor activity in Tg mice in various light conditions. In LD, wild-type controls showed both FAA and LD-entrained activities. In Tg mice, almost all activity was eventually consolidated to a single bout before the feeding time. The result suggests a possibility that in Tg mice the feeding cycle dominates the LD cycle as an entrainment agent. In constant darkness (DD), wild-type mice exhibited robust free-run activity and FAA during RF. For Tg mice, only the rhythm entrained to RF was observed in DD. Furthermore, after returning to free feeding, the free-run started from the RF-entrained phase. These results suggest that the SCN of Tg mice is entrainable to RF and that the mCRY1 mutation alters the sensitivity of SCN to the cycle of nonphotic zeitgebers.
authors.affiliation: Research Center for Molecular Genetics, Institute for Promotion of Medical Science Research, Faculty of Medicine, Yamagata University, Yamagata, 990-9585 Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okano
authors.affiliation: Division of Dynamic Proteome in Cancer and Aging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-8575 Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yasui
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Yamagata University, Yamagata, 990-9585 Japan ; Miyuki-Kai Hospital, Kaminoyama, 999-3161 Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Hayasaka
authors.affiliation: Research Center for Molecular Genetics, Institute for Promotion of Medical Science Research, Faculty of Medicine, Yamagata University, Yamagata, 990-9585 Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakajima
keywords: Circadian clock; Food-anticipatory activity; Food-entrainable oscillator; Interneuronal coupling; Nonphotic zeitgeber; Restricted feeding cycle; Suprachiasmatic nucleus