The involvement of Cry1 and Cry2 genes in the regulation of the circadian body temperature rhythm in mice

1 Department of Integrative Physiology, School of Human Sciences, Waseda University, Tokorozawa, Saitama; 2 Department of Physiology, School of Allied Health Sciences, Faculty of Medicine, Osaka University Suita, Osaka; 3 Clock Cell Biology Research Group, National Institute of Advanced Industrial Science and Technology, Institute for Biological Resources and Functions, Tsukuba, Ibaraki; and 4 Department of Physiology, School of Sports Sciences, Waseda University, Tokorozawa, Saitama, Japan Submitted 15 June 2004 ; accepted in final form 20 August 2004 The criptochrome genes ( Cry 1 and Cry 2) are involved in the molecular mechanism that controls the circadian clock, and mice lacking these genes ( Cry 1 –/– / Cry 2 –/– ) are behaviorally arrhythmic. It has been speculated that the circadian clock modulates the characteristics of thermoregulation, resulting in body temperature (T b ) rhythm. However, there is no direct evidence proving this speculation. We show here that T b and heat production in Cry 1 –/– / Cry 2 –/– mice are arrhythmic under constant darkness. In contrast, both rhythms occur under a light-dark cycle and/or periodical food restriction linked with spontaneous activity and/or eating, although they are not robust as those in wild-type mice. The relationship between heat production and T b in Cry 1 –/– / Cry 2 –/– mice is linear and identical under any conditions, indicating that their T b rhythm is determined by heat production rhythm associated with activity and eating. However, T b in wild-type mice is maintained at a relatively higher level in the active phase than the inactive phase regardless of the heat production level. These results indicate that the thermoregulatory responses are modulated according to the circadian phase, and the Cry genes are involved in this mechanism. circadian clock; thermoregulation; metabolism Address for reprint requests and other correspondence: K. Nagashima, Dept. of Integrative Physiology, School of Human Sciences, Waseda Univ., Mikajima 2–579-15, Tokorozawa, Saitama 359–1192, Japan (E-mail: k-nagashima{at}waseda.jp )