The tau mutation in the Syrian hamster resides in the enzyme casein kinase 1 
epsilon (CK1epsilon), resulting in a dramatic acceleration of wheel-running 
activity cycles to about 20 hours. tau also impacts growth, energy, metabolism, 
feeding behavior, and circadian mechanisms underpinning seasonal timing, causing 
accelerated reproductive and neuroendocrine responses to photoperiodic changes. 
Modeling and experimental studies suggest that tau acts as a gain of function on 
specific residues of PER, consistent with hamster studies showing accelerated 
degradation of PER in the suprachiasmatic nucleus in the early circadian night. 
We have created null and tau mutants of Ck1epsilon in mice. Circadian period 
lengthens in CK1epsilon(/), whereas CK1epsilon(tau/tau) shortens circadian 
period of behavior in vivo in a manner nearly identical to that of the Syrian 
hamster. CK1epsilon(tau/tau) also accelerates molecular oscillations in 
peripheral tissues, demonstrating its global circadian role. CK1epsilon(tau) 
acts by promoting degradation of both nuclear and cytoplasmic PERIOD, but not 
CRYPTOCHROME, proteins. Our studies reveal that tau acts as a gain-of-function 
mutation, to accelerate degradation of PERIOD proteins. tau has consistent 
effects in both hamsters and mice on the circadian organization of behavior and 
metabolism, highlighting the global impact of this mutation on mammalian 
clockwork in brain and periphery.