BACKGROUND: The cryptochrome 1 and 2 genes (cry1 and cry2) are necessary for the 
generation of circadian rhythms, as mice lacking both of these genes (cry1,2-/-) 
lack circadian rhythms. We studied sleep in cry1,2-/- mice under baseline 
conditions as well as under conditions of constant darkness and enforced 
wakefulness to determine whether cryptochromes influence sleep regulatory 
processes.
RESULTS: Under all three conditions, cry1,2-/- mice exhibit the hallmarks of 
high non-REM sleep (NREMS) drive (i.e., increases in NREMS time, NREMS 
consolidation, and EEG delta power during NREMS). This unexpected phenotype was 
associated with elevated brain mRNA levels of period 1 and 2 (per1,2), and 
albumin d-binding protein (dbp), which are known to be transcriptionally 
inhibited by CRY1,2. To further examine the relationship between circadian genes 
and sleep homeostasis, we examined wild type mice and rats following sleep 
deprivation and found increased levels of per1,2 mRNA and decreased levels of 
dbp mRNA specifically in the cerebral cortex; these changes subsided with 
recovery sleep. The expression of per3, cry1,2, clock, npas2, bmal1, and 
casein-kinase-1epsilon did not change with sleep deprivation.
CONCLUSIONS: These results indicate that mice lacking cryptochromes are not 
simply a genetic model of circadian arrhythmicity in rodents and functionally 
implicate cryptochromes in the homeostatic regulation of sleep.