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The Journal of Neuroscience, August 20, 2003, 23(20):7670-7676
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Cellular Location and Circadian Rhythm of Expression of the Biological Clock Gene Period 1 in the Mouse Retina
Paul Witkovsky,1,2 Eleonora Veisenberger,1 Joseph LeSauter,3 Lily Yan,7 Madeleine Johnson,4 Dao-Qi Zhang,6 Douglas McMahon,6 andRae Silver3,5,7 Departments of 1Ophthalmology and 2Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, 3Department of Psychology, Barnard College, New York, New York 10027, 4Graduate Training Program and 5Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, New York 10032, 6Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37027, and 7Department of Psychology, Columbia University, New York, New York 10027
The cellular location and rhythmic expression of Period 1 (Per1) circadian clock gene were examined in the retina of a Per1::GFP transgenic mouse. Mouse Per1 (mPer1) RNA was localized to inner nuclear and ganglion cell layers but was absent in the outer nuclear (photoreceptor) layer. Green fluorescent protein (GFP), which was shown to colocalize with PER1 protein, was found in a few subtypes of amacrine neuron, including those containing tyrosine hydroxylase, calbindin, and calretinin, but not in cholinergic amacrine cells. A small subset of ganglion cells also contained GFP immunoreactivity (GFP-IR), but the melanopsin-containing subtype, which projects to the suprachiasmatic nuclei (SCN), lacked GFP-IR. Although the intensity of GFP-IR varied among the populations of amacrine cells at each time point that was examined, both diurnal and circadian rhythms were found for the fraction of neurons showing strong GFP-IR, with peak expression between Zeitgeber/circadian (ZT/CT) times 10 and 14. In SCNs that were examined in the same mice used for the retinal measures, the peak in GFP-IR also occurred at approximately ZT/CT 10. Our results are the first to demonstrate a circadian rhythm of a biological clock component in identified neurons of a mammalian retina.
Key words: transgenic mouse; biological clock genes; retina; amacrine cell; melanopsin; circadian rhythm
Received Apr. 28, 2003; revised Jun. 19, 2003; accepted Jun. 26, 2003.
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