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Impaired light masking in dopamine D2 receptor–null mice

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Abstract

Disruption of overt circadian rhythms can occur without influencing the endogenous pacemaker, the so-called 'masking' effect classically elicited by light. As the physiological pathways involved in light masking remain elusive, we analyzed mice lacking the dopamine D2 receptor. Although circadian rhythmicity was normal, D2R-null mice showed a markedly deficient light masking response, indicating that D2R-mediated signaling is an essential component of the neuronal pathways leading to light masking of circadian rhythms.

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Figure 1: Defect in the masking response to light in D2R knockout mice.
Figure 2: Unimpaired photic response of SCN clock and pineal Aanat in D2R knockout mice.

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Acknowledgements

M.D. is supported by Japan Society for the Promotion of Science Postdoctoral Fellowships for Research Abroad; I.Y. by a fellowship from the Association pour la Recherche sur le Cancer; and J.H. by a fellowship from the Fondation pour la Recherche Médicale. This work and M.M. and E.T. were supported by the EC LSHM-CT-2004-005166 grant. Additional funds are from Fondation de France, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre Hospitalier Universitaire Régional, Fondation de la Recherche Médicale, Université Louis Pasteur, Electricité de France, Association pour la Recherche sur le Cancer and La Ligue Contre le Cancer.

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Author notes

  1. Masao Doi

    Present address: Division of Molecular Brain Science, Department of Brain Science, Kobe University Graduate School of Medicine, 7-5-1 Kusonoki-cho, Chuo-ku, Kobe, 650-0017, Japan

  2. Jun Hirayama & Paolo Sassone-Corsi

    Present address: Department of Pharmacology, University of California Irvine, Irvine, California, 92697, USA

  3. Monica Malerba, Emanuele Tirotta & Emiliana Borrelli

    Present address: Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, California, 92697, USA

Authors and Affiliations

  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 rue Laurent Fries 67404, Strasbourg, Illkirch, France

    Masao Doi, Irene Yujnovsky, Jun Hirayama, Monica Malerba, Emanuele Tirotta, Paolo Sassone-Corsi & Emiliana Borrelli

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  1. Masao Doi
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  2. Irene Yujnovsky
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Correspondence to Paolo Sassone-Corsi or Emiliana Borrelli.

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Supplementary information

Supplementary Fig. 1

Light induction of mPer1 is reduced in the retina of D2R knock-out mice. (PDF 189 kb)

Supplementary Fig. 2

Generation of a specific antibody against D2R. (PDF 270 kb)

Supplementary Fig. 3

Immunofluorescence showing the localisation of the D2 Receptor in the mouse retina. (PDF 587 kb)

Supplementary Fig. 4

Photic induction of mPer1 in the SCN. (PDF 187 kb)

Supplementary Fig. 5

Visually-driven behaviors of D2R−/− mice. (PDF 199 kb)

Supplementary Table 1

Phenotypic characteristics of D2R knock-out mice (PDF 69 kb)

Supplementary Methods (PDF 124 kb)

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Doi, M., Yujnovsky, I., Hirayama, J. et al. Impaired light masking in dopamine D2 receptor–null mice. Nat Neurosci 9, 732–734 (2006). https://doi.org/10.1038/nn1711

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  • DOI: https://doi.org/10.1038/nn1711

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