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Example sentences for: npas
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We assume that the effects on sleep we observed in cry1 , 2 -/-mice are a result of a lack of cryptochrome -dependent inhibition of the transcriptional activation provided by the bHLH-PAS heterodimers CLOCK:BMAL1 and NPAS2:BMAL1 [ 19 20 37 ] , although cryptochromes also play a role in stabilizing and nuclear sequestration of PER proteins [ 38 ] , and in photoreception [ 39 ] . Lack of cryptochromes results in increased mRNA levels of CLOCK/NPAS2:BMAL1 target genes, including the circadian genes per1 and per2 [ 20 23 ] . The expression of these two genes is viewed as a state variable of the molecular circadian clock or a marker of CLOCK/NPAS2:BMAL1-induced transcription, although at least per1 transcription can also be (rapidly) induced by light [ 40 41 ] , through a CREB-dependent signaling pathway [ 42 43 44 ] . The observation of high brain levels of per1,2 transcripts under baseline conditions in cry1,2 -/-mice raises the possibility that these or other CLOCK/NPAS2:BMAL1 target genes are involved in the homeostatic regulation of sleep.
We also measured the expression of five other circadian genes: bmal1 , clock , npas2 , per3 , and casein kinase -1-ε ( csnk1e ) in the cortex; the levels of these five mRNAs were not affected by SD (data not shown).
At least 90 genes are regulated in a similar fashion by NPAS2:BMAL1 [ 37 ] and the identity of the target genes critical for the NREMS phenotype in cry1,2 -/- mice remains to be determined.
For five other targets ( bmal1 , clock , npas2 , per3 , and csnk1e ), expression was quantified in the cortex only.
Finally, from a functional perspective, it is interesting that CLOCK/NPAS2:BMAL1 transcriptional activity is sensitive to redox state [ 24 ] . This transcriptional activity might thus provide a link between neuronal activity and an energy regulatory function for NREMS, as has been suggested previously [ 55 ] .
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