The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Per2  -  period circadian clock 2

Mus musculus

Synonyms: Circadian clock protein PERIOD 2, Period circadian protein homolog 2, mKIAA0347, mPER2, mPer2
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Per2

  • Here we report that Per2-deficient mice were more resistant to lipopolysaccharide (LPS)-induced endotoxic shock than control wild-type mice [1].
  • In our present study, we show that the rat C6 glioma cell line displays circadian oscillations of reporter luciferase bioluminescence driven by the mouse Per2 promoter and of clock-related gene transcripts [2].
  • The E2 enhancer accounts for most circadian transcriptional drive of the mPer2 locus by CLOCK:BMAL1, is a major site of DNaseI hypersensitivity in this region, and is constitutively bound by a transcriptional complex containing the CLOCK protein [3].

Psychiatry related information on Per2

  • What is more, we investigated voluntary alcohol consumption in Per2 ( Brdm1 ) mice with the results suggesting a relationship between this circadian clock gene and ethanol consumption [4].
  • Mice homozygous for the targeted allele of either mPer1 or mPer2 had severely disrupted locomotor activity rhythms during extended exposure to constant darkness [5].
  • Although mPer1 and mPer2 represent key elements of the molecular clock in the SCN, they are not required for homeostatic regulation of the daily amounts of waking, SWS, or REM sleep [6].
  • Here we show that the mouse homologues of the Drosophila Per gene, mPer1 and mPer2, modulate cocaine sensitization and reward, two phenomena extensively studied in humans and animals because of their importance for drug abuse [7].
  • Despite reported differences in maximal levels and timing of mCry1, mPer1, and mPer2 RNAs, the corresponding protein levels peaked simultaneously during late day, suggesting a codependency for their stabilization and/or nuclear entry [8].

High impact information on Per2

  • Moreover, the mutants fail to show acute induction of mPer1 and mPer2 by nocturnal illumination [9].
  • In particular, the transcription of c-myc is controlled directly by circadian regulators and is deregulated in the mPer2 mutant [10].
  • MOP4 exhibits a robust rhythm in the vasculature, and retinoic acid can phase shift Per2 mRNA rhythmicity in vivo and in serum-induced smooth muscle cells in vitro, providing a molecular mechanism for hormonal control of clock gene expression [11].
  • The mouse PERIOD proteins (mPER1 and mPER2), CLOCK, and BMAL1 undergo robust circadian changes in phosphorylation [12].
  • We demonstrate that Per2(Brdm1) mutant mice, which have a deletion in the PAS domain of the Per2 protein, show alterations in the glutamatergic system [13].

Biological context of Per2

  • The promoter regions of the Per1, Per2 and Cry1 genes exhibit circadian rhythms in H3 acetylation and RNA polymerase II binding that are synchronous with the corresponding steady-state messenger RNA rhythms [14].
  • Thus, mPER1 influences rhythmicity primarily through interaction with other clock proteins, while mPER2 positively regulates rhythmic gene expression, and there is partial compensation between products of these two genes [5].
  • Differences between the genotypes were seen in the 24-h distribution of sleep, reflecting especially the phase advance of motor activity onset observed in mPer2 mutants [15].
  • While the daily distribution of sleep was modulated by mPer1 and mPer2 genes, sleep homeostasis reflected by the SWA increase after 6-h SD was preserved in the mPer mutants [15].
  • Therefore, we blocked mPer translation using antisense phosphothioate oligonucleotides (ODNs) for mPer1 and mPer2 mRNAs and examined the effects on the circadian rhythm of cytosolic Ca2+ concentration and action potentials in SCN slice cultures [16].

Anatomical context of Per2

  • Mammalian circadian clock genes Per1 and Per2 are rhythmically expressed not only in the suprachiasmatic nucleus where the mammalian circadian clock exists, but also in other brain regions and peripheral tissues [17].
  • In this experiment, we examined the day--night pattern of expression of Per1 and Per2 mRNA in the mouse SCN and cerebral cortex on embryonic day 17, postnatal day 3, and in young adult mice under a light-dark cycle [18].
  • Per2 expression in these cocultured fibroblasts exhibited a similar reduction in peak levels, but was marked by non-24 h or irregular peak-to-peak intervals [19].
  • 1. Per2 and Per3 genes were both localized to microchromosomes. qClock mRNA was expressed throughout the day, while qPer2 and qPer3 showed robust circadian oscillation in the eye and the pineal gland [20].
  • Our data suggest that Per2 is an important regulator of NK cell function, therefore providing the first direct link between the circadian clock system and innate immune responses [1].

Associations of Per2 with chemical compounds

  • Previously, our lab demonstrated the involvement of mouse Per1 (mPer1) and Per2 (mPer2) in modulating cocaine sensitization and reward [4].
  • Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock [5].
  • CONCLUSIONS: Contrary to the mPer2 data, the present findings do not suggest a relationship between the circadian clock gene mPer1 and ethanol reinforcement, seeking, and relapse behavior [4].
  • The present results suggest that the daily oscillation of mPer1 but not of mPer2 in the SCN in fetal and early postnatal mice may be associated with the daily rhythms of 2-deoxyglucose uptake and neuronal firing [18].
  • Collectively, these data establish glutamate as a link between dysfunction of the circadian clock gene Per2 and enhanced alcohol intake [13].

Regulatory relationships of Per2

  • Furthermore, mPer2 is co-expressed with mPer1 in single SCN cells [21].

Other interactions of Per2

  • The mPER3 protein shows approximately 37% amino acid identity with mPER1 and mPER2 proteins [22].
  • Similar to changes in molecular and physiological rhythmicity observed in the SCN of Clock mutant mice, the rhythmic pattern of Per2 expression was disrupted and the period of metabolic rhythmicity was increased in SCN2.2 cells subjected to antisense inhibition of Clock [19].
  • The phase of Per2 and Bmal1 expression remained unchanged regardless of feeding condition [23].
  • Here, a decrease of positive feedback strength associated with mutating the Per2 gene is compensated by the Cry2-/- mutation that simultaneously decreases the negative feedback strength [24].
  • Lesion of the suprachiasmatic nucleus, the location of the main clock system, led to loss of Per2 and Pai-1 daily expression profiles [25].

Analytical, diagnostic and therapeutic context of Per2

  • We demonstrated that mPer1, but not mPer2, mRNA expression was dependent on the depolarization state controlled by extracellular KCl concentration in the granule cell culture [17].
  • To study the rhythmic expression of Per in the Xenopus retina, we used a degenerate RT-PCR strategy to obtain cDNA clones covering the entire 1427 amino acid coding region of a Xenopus homologue of Per2 and a partial cDNA sequence for a Xenopus homologue of Per1 [26].
  • Our precise quantitative in situ hybridizations have revealed that the peak expression of mPer2 transcripts is delayed by 8 h in LD (light-dark) or 4 h in DD (dark-dark) conditions when compared to mPer1 [21].
  • Sympathetic nerve denervation by 6-hydroxydopamine flattened the daily rhythm of mPer1 and mPer2 gene expression [27].
  • Quantitative real-time PCR analysis revealed that alphaMUPA mice exhibit robust expression of the clock genes mPer1, mPer2, mClock, and mCry1 but not mBmal1 in the liver [28].


  1. The circadian clock Period 2 gene regulates gamma interferon production of NK cells in host response to lipopolysaccharide-induced endotoxic shock. Liu, J., Mankani, G., Shi, X., Meyer, M., Cunningham-Runddles, S., Ma, X., Sun, Z.S. Infect. Immun. (2006) [Pubmed]
  2. Circadian rhythm generation in a glioma cell line. Fujioka, A., Takashima, N., Shigeyoshi, Y. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  3. A noncanonical E-box enhancer drives mouse Period2 circadian oscillations in vivo. Yoo, S.H., Ko, C.H., Lowrey, P.L., Buhr, E.D., Song, E.J., Chang, S., Yoo, O.J., Yamazaki, S., Lee, C., Takahashi, J.S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. Ethanol self-administration and reinstatement of ethanol-seeking behavior in Per1 ( Brdm1 ) mutant mice. Zghoul, T., Abarca, C., Sanchis-Segura, C., Albrecht, U., Schumann, G., Spanagel, R. Psychopharmacology (Berl.) (2007) [Pubmed]
  5. Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock. Bae, K., Jin, X., Maywood, E.S., Hastings, M.H., Reppert, S.M., Weaver, D.R. Neuron (2001) [Pubmed]
  6. Sleep rhythmicity and homeostasis in mice with targeted disruption of mPeriod genes. Shiromani, P.J., Xu, M., Winston, E.M., Shiromani, S.N., Gerashchenko, D., Weaver, D.R. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2004) [Pubmed]
  7. Cocaine sensitization and reward are under the influence of circadian genes and rhythm. Abarca, C., Albrecht, U., Spanagel, R. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  8. Rhythms in clock proteins in the mouse pars tuberalis depend on MT1 melatonin receptor signalling. Jilg, A., Moek, J., Weaver, D.R., Korf, H.W., Stehle, J.H., von Gall, C. Eur. J. Neurosci. (2005) [Pubmed]
  9. The VPAC(2) receptor is essential for circadian function in the mouse suprachiasmatic nuclei. Harmar, A.J., Marston, H.M., Shen, S., Spratt, C., West, K.M., Sheward, W.J., Morrison, C.F., Dorin, J.R., Piggins, H.D., Reubi, J.C., Kelly, J.S., Maywood, E.S., Hastings, M.H. Cell (2002) [Pubmed]
  10. The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Fu, L., Pelicano, H., Liu, J., Huang, P., Lee, C. Cell (2002) [Pubmed]
  11. Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock. McNamara, P., Seo, S.P., Rudic, R.D., Sehgal, A., Chakravarti, D., FitzGerald, G.A. Cell (2001) [Pubmed]
  12. Posttranslational mechanisms regulate the mammalian circadian clock. Lee, C., Etchegaray, J.P., Cagampang, F.R., Loudon, A.S., Reppert, S.M. Cell (2001) [Pubmed]
  13. The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption. Spanagel, R., Pendyala, G., Abarca, C., Zghoul, T., Sanchis-Segura, C., Magnone, M.C., Lascorz, J., Depner, M., Holzberg, D., Soyka, M., Schreiber, S., Matsuda, F., Lathrop, M., Schumann, G., Albrecht, U. Nat. Med. (2005) [Pubmed]
  14. Rhythmic histone acetylation underlies transcription in the mammalian circadian clock. Etchegaray, J.P., Lee, C., Wade, P.A., Reppert, S.M. Nature (2003) [Pubmed]
  15. Homeostatic sleep regulation is preserved in mPer1 and mPer2 mutant mice. Kopp, C., Albrecht, U., Zheng, B., Tobler, I. Eur. J. Neurosci. (2002) [Pubmed]
  16. mPer2 antisense oligonucleotides inhibit mPER2 expression but not circadian rhythms of physiological activity in cultured suprachiasmatic nucleus neurons. Sugiyama, T., Yoshioka, T., Ikeda, M. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  17. Calcium and pituitary adenylate cyclase-activating polypeptide induced expression of circadian clock gene mPer1 in the mouse cerebellar granule cell culture. Akiyama, M., Minami, Y., Nakajima, T., Moriya, T., Shibata, S. J. Neurochem. (2001) [Pubmed]
  18. Differential daily expression of Per1 and Per2 mRNA in the suprachiasmatic nucleus of fetal and early postnatal mice. Shimomura, H., Moriya, T., Sudo, M., Wakamatsu, H., Akiyama, M., Miyake, Y., Shibata, S. Eur. J. Neurosci. (2001) [Pubmed]
  19. Effects of altered Clock gene expression on the pacemaker properties of SCN2.2 cells and oscillatory properties of NIH/3T3 cells. Allen, G.C., Farnell, Y., Bell-Pedersen, D., Cassone, V.M., Earnest, D.J. Neuroscience (2004) [Pubmed]
  20. Molecular analysis of avian circadian clock genes. Yoshimura, T., Suzuki, Y., Makino, E., Suzuki, T., Kuroiwa, A., Matsuda, Y., Namikawa, T., Ebihara, S. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  21. A new mammalian period gene predominantly expressed in the suprachiasmatic nucleus. Takumi, T., Matsubara, C., Shigeyoshi, Y., Taguchi, K., Yagita, K., Maebayashi, Y., Sakakida, Y., Okumura, K., Takashima, N., Okamura, H. Genes Cells (1998) [Pubmed]
  22. Three period homologs in mammals: differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain. Zylka, M.J., Shearman, L.P., Weaver, D.R., Reppert, S.M. Neuron (1998) [Pubmed]
  23. Feeding cues alter clock gene oscillations and photic responses in the suprachiasmatic nuclei of mice exposed to a light/dark cycle. Mendoza, J., Graff, C., Dardente, H., Pevet, P., Challet, E. J. Neurosci. (2005) [Pubmed]
  24. Modeling feedback loops of the Mammalian circadian oscillator. Becker-Weimann, S., Wolf, J., Herzel, H., Kramer, A. Biophys. J. (2004) [Pubmed]
  25. Cholesterol diet enhances daily rhythm of Pai-1 mRNA in the mouse liver. Kudo, T., Nakayama, E., Suzuki, S., Akiyama, M., Shibata, S. Am. J. Physiol. Endocrinol. Metab. (2004) [Pubmed]
  26. Differential regulation of two period genes in the Xenopus eye. Zhuang, M., Wang, Y., Steenhard, B.M., Besharse, J.C. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  27. Adrenergic regulation of clock gene expression in mouse liver. Terazono, H., Mutoh, T., Yamaguchi, S., Kobayashi, M., Akiyama, M., Udo, R., Ohdo, S., Okamura, H., Shibata, S. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  28. Long-lived {alpha}MUPA transgenic mice exhibit pronounced circadian rhythms. Froy, O., Chapnik, N., Miskin, R. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
WikiGenes - Universities