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

The criptochrome genes (Cry1 and Cry2) are involved in the molecular mechanism that controls the circadian clock, and mice lacking these genes (Cry1^-/-/Cry2^-/-) 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 Cry1^-/-/Cry2^-/- 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 Cry1 ^-/-/Cry2^-/- 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.