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Am J Physiol Regul Integr Comp Physiol (August 26, 2004). doi:10.1152/ajpregu.00395.2004
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Submitted on June 15, 2004
Accepted on August 20, 2004

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

Kei Nagashima1*, Kenta Matsue2, Masahiro Konishi2, Chisato Iidaka3, Koyomi Miyazaki3, Norio Ishida3, and Kazuyuki Kanosue4

1 Department of Integrative Physiology, Waseda University, School of Human Sciences, Tokorozawa, Saitama, Japan; Department of Integrative Physiology, Osaka University, School of Allied Health Sciences, Suita, Osaka, Japan
2 Department of Integrative Physiology, Osaka University, School of Allied Health Sciences, Suita, Osaka, Japan
3 Clock Cell Biology Research Group, Nationla Institute of Advanced Industrial Science and Technology, Institute for Biological Resources and Functions, Tsukuba-shi, Ibaraki, Japan
4 Department of Physiology, Waseda University, School of Sports Sciences, Tokorozawa, Saitama, Japan

* To whom correspondence should be addressed. E-mail: k-nagashima{at}waseda.jp.

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 (Tb) rhythm. However, there is no direct evidence proving this speculation. We show here that Tb 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 Tb in Cry1-/-/Cry2-/- mice is linear and identical under any conditions, indicating that their Tb rhythm is determined by heat production rhythm associated with activity and eating. However, Tb 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.




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