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  Genetic background-dependent effects of murine micro RNAs on circadian clock function.

Kießling, S., Ucar, A., Chowdhury, K., Oster, H., & Eichele, G. (2017). Genetic background-dependent effects of murine micro RNAs on circadian clock function. PLoS One, 12(4): e0176547. doi:10.1371/journal.pone.0176547.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-2F02-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-2F05-3
Genre: Journal Article

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 Creators:
Kießling, S.1, Author              
Ucar, A., Author
Chowdhury, K.2, Author              
Oster, H.3, Author              
Eichele, G.1, Author              
Affiliations:
1Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society, escidoc:persistent34              
2Facility of Microarray Analyses, MPI for biophysical chemistry, Max Planck Society, escidoc:578589              
3Research Group of Circadian Rhythms, MPI for biophysical chemistry, Max Planck Society, escidoc:578594              

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 Abstract: MicroRNAs (miRs) are important regulators of a wide range of biological processes. Antagomir studies suggest an implication of miR-132 in the functionality of the mammalian circadian clock. miR-212 and miR-132 are tandemly processed from the same transcript and share the same seed region. We found the clock modulator miR-132 and miR-212 to be expressed rhythmically in the central circadian clock. Consequently, mRNAs implicated in circadian functions may likely be targeted by both miRs. To further characterize the circadian role we generated mice with stable deletion of the miR-132/212 locus and compared the circadian behavior of mutant and wild-type control animals on two genetic backgrounds frequently used in chronobiological research, C57BL/6N and 129/Sv. Surprisingly, the wheel-running activity phenotype of miR mutant mice was highly background specific. A prolonged circadian free-running period in constant darkness was found in 129/Sv, but not in C57BL/6N miR-132/212 knockout mice. In contrast, in C57BL/6N, but not in 129/Sv miRNA132/212 knockout mice a lengthened free-running period was observed in constant light conditions. Furthermore, miR-132/212 knockout mice on 129/Sv background exhibited enhanced photic phase shifts of locomotor activity accompanied by reduced light induction of Period gene transcription in the SCN. This phenotype was absent in miRNA-132/212 knockout mice on a C57BL/6N background. Together, our results reveal a strain and light regimen-specific function of miR-132/212 in the circadian clock machinery suggesting that miR-132 and miR-212 act as background-dependent circadian rhythm modulators.

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Language(s): eng - English
 Dates: 2017-04-27
 Publication Status: Published online
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 Rev. Method: Internal
 Identifiers: DOI: 10.1371/journal.pone.0176547
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Title: PLoS One
Source Genre: Journal
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Pages: 16 Volume / Issue: 12 (4) Sequence Number: e0176547 Start / End Page: - Identifier: -