Loss of circadian rhythmicity in agingmPer1-/-mCry2-/-mutant mice
Open Access
- 1 June 2003
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 17 (11), 1366-1379
- https://doi.org/10.1101/gad.256103
Abstract
ThemPer1, mPer2, mCry1, andmCry2genes play a central role in the molecular mechanism driving the central pacemaker of the mammalian circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus. In vitro studies suggest a close interaction of all mPER and mCRY proteins. We investigated mPER and mCRY interactions in vivo by generating different combinations ofmPer/mCrydouble-mutant mice. We previously showed thatmCry2acts as a nonallelic suppressor ofmPer2in the core clock mechanism. Here, we focus on the circadian phenotypes ofmPer1/mCrydouble-mutant animals and find a decay of the clock with age inmPer1-/-mCry2-/-mice at the behavioral and the molecular levels. Our findings indicate that complexes consisting of different combinations of mPER and mCRY proteins are not redundant in vivo and have different potentials in transcriptional regulation in the system of autoregulatory feedback loops driving the circadian clock.Keywords
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