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

Abstract

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.

Cross-talks between Circadian Timing System and Cell Division Cycle Determine Cancer Biology and Therapeutics

“…However, the in vivo part of this study was performed in double-mutant mice kept in LD 12:12, an environmental condition that dampens, yet does not disrupt, 24-hour physiology, whereas DD exposure does 468 LÉVI ET AL. (Nagashima et al 2005). Cultured fibroblasts from the Cry double mutants also did not display an altered response to radiation exposure (Gauger and Sancar 2005).…”

Attenuated Circadian Rhythms in Mice Lacking theProkineticin 2Gene

“…A radio transmitter device (G2 Emitter; Mini-Mitter, Sunriver, OR) used to measure body temperature was implanted in the abdominal cavity by sterile technique under general anesthesia (Nagashima et al, 2005). Body temperature was recorded by a receiver board (ER-4000 energizer receiver) underneath the cage and were stored in a personal computer every 5 min.…”

“…Ϫ/Ϫ mice The body temperature in mammals also exhibits a circadian rhythm, which is at least in part controlled by signals from the SCN (Moore, 1997;Schibler and Sassone-Corsi, 2002;Nagashima et al, 2005). The core body temperature is higher in the active phase than inactive phase even under constant darkness.…”

“…It has been proposed that behavioral or physiological rhythms such as locomotor activity and/or food intake may account for body temperature rhythms. However, the SCN is also able to modulate thermoregulation that results in body temperature rhythm, because the circadian body temperature rhythm persists in completely bed-rested humans, fasting humans and rats, and hibernating squirrels (Nagashima et al, 2005). We implanted body temperature probes (Mini-Mitter) into the abdominal cavities of PK2 Ϫ/Ϫ and WT mice (n ϭ 5 mice per group), and the core body temperature was monitored continuously under LD conditions.…”

Concepts to utilize in describing thermoregulation and neurophysiological evidence for how the system works

“…Various concepts and advances in the research field of temperature regulation set the stage for the current era, which has involved a detailed characterization of the system, and furthered understanding of the involved nervous structures and effector organs (Nakayama 1985;Nagashima et al 2000;Kanosue et al 2001;Morrison et al 2008;Nakamura and Morrison 2008a, b;Tanaka et al 2009). Interactions between thermal homeostasis and other systems have also received careful analysis, such as during fasting and dehydration (Yoda et al 2000;Nagashima et al 2001Nagashima et al , 2003Nagashima et al , 2005Konishi et al 2002Konishi et al , 2003. In addition to internal systems involved in temperature regulation, the external environment has a definite effect on the body temperature.…”