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Gene Review

Per1  -  period circadian clock 1

Mus musculus

Synonyms: Circadian clock protein PERIOD 1, Circadian pacemaker protein Rigui, Per, Period circadian protein homolog 1, Rigui, ...
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Disease relevance of Per1


Psychiatry related information on Per1

  • Mice homozygous for the targeted allele of either mPer1 or mPer2 had severely disrupted locomotor activity rhythms during extended exposure to constant darkness [6].
  • 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 [7].
  • 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 [8].
  • The role of mPer1 in morphine dependence in mice [9].
  • 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 [10].

High impact information on Per1

  • Mice lacking molecular-clock components (Per and Cry), or lacking Per genes in osteoblasts, display high bone mass, suggesting that bone remodeling may also be subject to circadian regulation [11].
  • Moreover, Per-deficient mice experience a paradoxical increase in bone mass following leptin intracerebroventricular infusion [11].
  • Moreover, the mutants fail to show acute induction of mPer1 and mPer2 by nocturnal illumination [12].
  • Bmal1 and Per transcription cycles display nearly opposite phases and are thus governed by different mechanisms [13].
  • Mice carrying a null mutation in the Period 1 (mPer1) gene were generated using embryonic stem cell technology [14].

Chemical compound and disease context of Per1


Biological context of Per1


Anatomical context of Per1

  • Per1 expression is not altered in testes from Clock mutant mice, suggesting that CLOCK does not activate Per1 in male germ cells, in contrast to what it does in other mouse tissues [18].
  • Strikingly, Per1 is restricted primarily to step 7 to 10 spermatids and thus appears to be developmentally regulated [18].
  • 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 [21].
  • 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 [22].
  • Although the caudate/putamen (CPu) expresses mPer1 and/or mPer2 mRNA, the function of these genes in this nucleus has not yet been elucidated [23].

Associations of Per1 with chemical compounds


Regulatory relationships of Per1


Other interactions of Per1

  • The magnitude and time course of acute light induction in the suprachiasmatic nuclei of the only known light-induced core clock genes, Per1 and Per2, are not affected by the Clock/+ mutation [30].
  • Furthermore, Per1 and Cry2 oscillations in the SCN were phase advanced by 1 and 3 h, respectively, in hypocalorie- but not in normocalorie-fed mice [31].
  • Transcript levels for each of these five genes fall at the two-cell stage, but are restored rapidly for Per1, Cry1 and Bmal1, presumptively by zygotic gene expression [32].
  • Three putative mammalian homologues (mPer1, mPer2 and mPer3) of the Drosophila circadian clock gene period (per) have been identified [33].
  • The aim of the study was to test whether mPer, mCry, Clock, and Bmal1 are rhythmically expressed in the mouse PT and how the absence of melatonin receptors affects clock gene expression [34].

Analytical, diagnostic and therapeutic context of Per1

  • RNase protection assay and in situ hybridization revealed in both strains a rhythm in transcript levels for Per1 with a peak at zeitgeber time (ZT) 08, but not for Cry2 [19].
  • The induced circadian oscillation of Per genes after treatment with high concentrations of serum or various drugs in cultured cells suggests the ubiquitous existence of the oscillatory mechanism [21].
  • We used a dispersed primary cell culture made up of mouse cerebellar granule cells to examine the stimuli inducing the mPer genes and their signaling pathways in neuronal tissues expressing mPer genes [21].
  • The genotypes did not differ in the effect of SD on the occipital EEG, while the effect on the frontal EEG was initially diminished in both mPer mutants [35].
  • Mice were injected (s.c.) with fluorogold (FG) in order to label neuroendocrine cells and brain sections were double-labelled for either FG and Per1 mRNA (labelled by GFP immunostaining) or FG and PER1 protein using fluorescence immunocytochemistry [36].


  1. Involvement of calcium/calmodulin-dependent protein kinase II in the induction of mPer1. Nomura, K., Takeuchi, Y., Yamaguchi, S., Okamura, H., Fukunaga, K. J. Neurosci. Res. (2003) [Pubmed]
  2. Cellular location and circadian rhythm of expression of the biological clock gene Period 1 in the mouse retina. Witkovsky, P., Veisenberger, E., LeSauter, J., Yan, L., Johnson, M., Zhang, D.Q., McMahon, D., Silver, R. J. Neurosci. (2003) [Pubmed]
  3. Simultaneous presence, in one serum, of four monoclonal antibodies that might correspond to different steps in a clonal evolution from polyreactive to monoreactive antibodies. Houdayer, M., Bouvet, J.P., Wolff, A., Magnac, C., Guillemot, J.C., Borche, L., Dighiero, G. J. Immunol. (1993) [Pubmed]
  4. Glutathione conjugation of perchloroethylene in rats and mice in vitro: sex-, species-, and tissue-dependent differences. Lash, L.H., Qian, W., Putt, D.A., Desai, K., Elfarra, A.A., Sicuri, A.R., Parker, J.C. Toxicol. Appl. Pharmacol. (1998) [Pubmed]
  5. The mPer1 clock gene expression in the rd mouse suprachiasmatic nucleus is affected by the retinal degeneration. Alvarez-López, C., Cernuda-Cernuda, R., García-Fernández, J.M. Brain Res. (2006) [Pubmed]
  6. 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]
  7. 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]
  8. 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]
  9. The role of mPer1 in morphine dependence in mice. Liu, Y., Wang, Y., Wan, C., Zhou, W., Peng, T., Liu, Y., Wang, Z., Li, G., Cornelisson, G., Halberg, F. Neuroscience (2005) [Pubmed]
  10. 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]
  11. The molecular clock mediates leptin-regulated bone formation. Fu, L., Patel, M.S., Bradley, A., Wagner, E.F., Karsenty, G. Cell (2005) [Pubmed]
  12. 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]
  13. The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Preitner, N., Damiola, F., Lopez-Molina, L., Zakany, J., Duboule, D., Albrecht, U., Schibler, U. Cell (2002) [Pubmed]
  14. Nonredundant roles of the mPer1 and mPer2 genes in the mammalian circadian clock. Zheng, B., Albrecht, U., Kaasik, K., Sage, M., Lu, W., Vaishnav, S., Li, Q., Sun, Z.S., Eichele, G., Bradley, A., Lee, C.C. Cell (2001) [Pubmed]
  15. Glutathione conjugation of perchloroethene in subcellular fractions from rodent and human liver and kidney. Dekant, W., Birner, G., Werner, M., Parker, J. Chem. Biol. Interact. (1998) [Pubmed]
  16. Rhythmic histone acetylation underlies transcription in the mammalian circadian clock. Etchegaray, J.P., Lee, C., Wade, P.A., Reppert, S.M. Nature (2003) [Pubmed]
  17. Circadian and light-induced transcription of clock gene Per1 depends on histone acetylation and deacetylation. Naruse, Y., Oh-hashi, K., Iijima, N., Naruse, M., Yoshioka, H., Tanaka, M. Mol. Cell. Biol. (2004) [Pubmed]
  18. No circadian rhythms in testis: Period1 expression is clock independent and developmentally regulated in the mouse. Morse, D., Cermakian, N., Brancorsini, S., Parvinen, M., Sassone-Corsi, P. Mol. Endocrinol. (2003) [Pubmed]
  19. Clock gene expression in the retina of melatonin-proficient (C3H) and melatonin-deficient (C57BL) mice. Dinet, V., Ansari, N., Torres-Farfan, C., Korf, H.W. J. Pineal Res. (2007) [Pubmed]
  20. Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock. Lee, C., Weaver, D.R., Reppert, S.M. Mol. Cell. Biol. (2004) [Pubmed]
  21. 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]
  22. 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]
  23. Sensitized increase of period gene expression in the mouse caudate/putamen caused by repeated injection of methamphetamine. Nikaido, T., Akiyama, M., Moriya, T., Shibata, S. Mol. Pharmacol. (2001) [Pubmed]
  24. 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]
  25. Physical and inflammatory stressors elevate circadian clock gene mPer1 mRNA levels in the paraventricular nucleus of the mouse. Takahashi, S., Yokota, S., Hara, R., Kobayashi, T., Akiyama, M., Moriya, T., Shibata, S. Endocrinology (2001) [Pubmed]
  26. 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]
  27. Dec1 and Dec2 expression is disrupted in the suprachiasmatic nuclei of Clock mutant mice. Butler, M.P., Honma, S., Fukumoto, T., Kawamoto, T., Fujimoto, K., Noshiro, M., Kato, Y., Honma, K. J. Biol. Rhythms (2004) [Pubmed]
  28. Acute physical stress elevates mouse period1 mRNA expression in mouse peripheral tissues via a glucocorticoid-responsive element. Yamamoto, T., Nakahata, Y., Tanaka, M., Yoshida, M., Soma, H., Shinohara, K., Yasuda, A., Mamine, T., Takumi, T. J. Biol. Chem. (2005) [Pubmed]
  29. Induction of PER1 mRNA expression in immortalized gonadotropes by gonadotropin-releasing hormone (GnRH): involvement of protein kinase C and MAP kinase signaling. Olcese, J., Sikes, H.E., Resuehr, D. Chronobiol. Int. (2006) [Pubmed]
  30. The mouse Clock mutation reduces circadian pacemaker amplitude and enhances efficacy of resetting stimuli and phase-response curve amplitude. Vitaterna, M.H., Ko, C.H., Chang, A.M., Buhr, E.D., Fruechte, E.M., Schook, A., Antoch, M.P., Turek, F.W., Takahashi, J.S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  31. 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]
  32. Circadian clockwork genes are expressed in the reproductive tract and conceptus of the early pregnant mouse. Johnson, M.H., Lim, A., Fernando, D., Day, M.L. Reprod. Biomed. Online (2002) [Pubmed]
  33. The mPer2 gene encodes a functional component of the mammalian circadian clock. Zheng, B., Larkin, D.W., Albrecht, U., Sun, Z.S., Sage, M., Eichele, G., Lee, C.C., Bradley, A. Nature (1999) [Pubmed]
  34. Melatonin plays a crucial role in the regulation of rhythmic clock gene expression in the mouse pars tuberalis. VON Gall, C., Weaver, D.R., Moek, J., Jilg, A., Stehle, J.H., Korf, H.W. Ann. N. Y. Acad. Sci. (2005) [Pubmed]
  35. Homeostatic sleep regulation is preserved in mPer1 and mPer2 mutant mice. Kopp, C., Albrecht, U., Zheng, B., Tobler, I. Eur. J. Neurosci. (2002) [Pubmed]
  36. Expression of the circadian clock gene Period 1 in neuroendocrine cells: an investigation using mice with a Per1::GFP transgene. Kriegsfeld, L.J., Korets, R., Silver, R. Eur. J. Neurosci. (2003) [Pubmed]
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