JOURNAL OF BIOLOGICAL RHYTHMS / December 2002Spoelstra et al. / SELF-SUSTAINED CIRCA IAN RHYTHMICITY Restoration of Self-Sustained Circadian Rhythmicity by the Mutant Clock Allele in Mice in Constant Illumination

Abstract Mice mutant for the Clock gene display abnormal circadian behavior characterized by long circadian periods and a tendency to become rapidly arrhythmic in constant darkness (DD). To investigate whether this result is con-tingent on the absence of light, the authors studied the circadian behavior of homozygous Clock mutant mice under conditions of both constant light and DD. Fourteen of 15 Clock/Clock mice stayed rhythmic in constant light of 70 to 170 lux, where 10 of 15 wild-type mice became arrhythmic. In contrast, only 5 of 15 Clock/ Clock mice and 15 of 15 wild-type mice remained rhythmic after 60 cycles when released in DD (dim red light of < 1.5 lux) after 8 days of entrainment. The resto-ration of self-sustained rhythmicity by the Clock allele cannot be attributed to reduced sensitivity of the system to light. It underscores the fact that self-sustain-ment is not a secure guide to functional organization. Key words circadian clock, constant illumination, Clock, mouse mutants, circadian rhythmicity Self-sustained rhythmicity in constant conditions i