Deletion of the mammalian circadian clock gene BMAL1/Mop3 alters baseline sleep architecture and the response to sleep deprivation.
OBJECTIVE
The finding that deletion or mutation of core circadian clock genes in both mice and flies induce unexpected alterations in sleep amount, sleep architecture and the recovery response to sleep deprivation, has led to new insights into functions of the circadian system that extend beyond its role as a regulator of the timing of the sleep-wake cycle. A key transcription factor in the transcriptional/translational feedback loop of mammalian circadian genes is BMAL1/Mop3, a heterodimeric partner to CLOCK. It was previously shown that mice deficient in the BMAL1/Mop3 gene become immediately arrhythmic in constant darkness and have reduced locomotor activity levels under entrained and constant conditions. In this study, we tested the hypothesis that the mammalian BMAL1/Mop3 gene would have regulatory effects on sleep-wake patterns.


METHODS
In mice with targeted deletion of the BMAL1/Mop3 gene, EEG/EMG sleep-wake patterns were recorded under entrained and free-running conditions as well as following acute (6-hrs) sleep deprivation.


RESULTS
Mice homozygous for the BMAL1/Mop3 deletion showed an attenuated rhythm of sleep and wakefulness distribution across the 24-hr period. In addition, these mice showed increases in total sleep time, sleep fragmentation and EEG delta power under baseline conditions, and an attenuated compensatory response to acute sleep deprivation.


CONCLUSIONS
These new data strengthen the hypothesis that molecular components of the circadian system play a central role in the generation of sleep and wakefulness beyond just the timing of these behavioral vigilance states.
Laposky
Aaron
A
Neurobiology and Physiology, Northwestern University, 2205 Tech Drive Hogan 2-160, Evanston, IL 60208-3520, USA. a-laposky@northwestern.edu
Easton
Amy
A
Dugovic
Christine
C
Walisser
Jacqueline
J
Bradfield
Christopher
C
Turek
Fred
F
D056930:ARNTL Transcription Factors; D000483:Alleles; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001831:Body Temperature / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D004569:Electroencephalography; D004576:Electromyography; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017286:Polysomnography; D012892:Sleep Deprivation / Q000235:genetics*; D012894:Sleep Stages / Q000502:physiology; D012895:Sleep, REM / Q000502:physiology
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; C538961:Bmal1 protein, mouse