( BMAL1 in the presence and absence of D...)Researchers Investigate Gene Linked With Circadian Liver Clock,Health

BMAL1 in the presence and absence of Dox, they found arrhythmic expression of most of the targeted clock genes when the liver clocks stopped, as expected. However, some genes, including the known clock gene mPer2 displayedrhythmic expression even when Bmal1 was inactive. This is noteworthy because in brain tissue from transgenic mice lacking Bmal1, mPer2 transcripts in SCN neurons are barely noticeable during the course of a day.

It’s possible that mPer2 transcription is more dependent on BMAL1 in the SCN than it is in the liver, however the authors considered two other explanations for the observed mPer2 activity: either the mice that didn’t eat Dox still harbored enough BMAL1 to drive cyclic mPer2 expression or oscillating systemic signals were responsible. To distinguish between these, they analyzed temporal mPer2 expression in isolation from master pacemaker signals by removing liver slices from mice carrying a fluorescent protein attached to mPer2. With this approach, luminescence signals showed a rhythmic profile that follows mPer2 activity.

The authors bred the mouse strain with the conditionally active liver clock with a strain carrying the mPer2 fusion gene. As expected, liver slices from the offspring without Dox did not exhibit circadian mPer2 expression; the liver oscillators had therefore been shut off. However, when Dox was added to the medium supporting the liver tissue, circadian rhythms matched those seen in livers from mice with fluorescent mPer2 and unimpeded Bmal1 expression. The mPer2 expression patterns in the liver explants together with in livers taken from the transgenic offspring show that liver oscillators can drive circadian gene expression in the absence of systemic cues and that systemic cues can do so in the absence of liver oscillators.

Among the other genes identified as being expressed in both mice fed on Dox or on normal diets were a number of heat-shock proteins (HSPs). In fact, heat-shock and mPe
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