{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:21:13Z","timestamp":1791264073511,"version":"4.1.0"},"reference-count":38,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5413","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[1999,4,16]]},"abstract":"<jats:p>\n            In mammals, ocular photoreceptors mediate an acute inhibition of pineal melatonin by light. The effect of rod and cone loss on this response was assessed by combining the\n            <jats:italic>rd<\/jats:italic>\n            mutation with a transgenic ablation of cones (\n            <jats:italic>cl<\/jats:italic>\n            ) to produce mice lacking both photoreceptor classes. Despite the loss of all known retinal photoreceptors,\n            <jats:italic>rd\/rd cl<\/jats:italic>\n            mice showed normal suppression of pineal melatonin in response to monochromatic light of wavelength 509 nanometers. These data indicate that mammals have additional ocular photoreceptors that they use in the regulation of temporal physiology.\n          <\/jats:p>","DOI":"10.1126\/science.284.5413.505","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:45:50Z","timestamp":1027763150000},"page":"505-507","source":"Crossref","is-referenced-by-count":442,"title":["Regulation of the Mammalian Pineal by Non-rod, Non-cone, Ocular Photoreceptors"],"prefix":"10.1126","volume":"284","author":[{"given":"Robert J.","family":"Lucas","sequence":"first","affiliation":[{"name":"Department of Biology, Sir Alexander Fleming Building, Imperial College of Science, Technology and Medicine, London, SW7 2AZ, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie S.","family":"Freedman","sequence":"additional","affiliation":[{"name":"Department of Biology, Sir Alexander Fleming Building, Imperial College of Science, Technology and Medicine, London, SW7 2AZ, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Mun\u0303oz","sequence":"additional","affiliation":[{"name":"Departmento de Morfologia y Biologia Cellular, Universidad de Oviedo, Oviedo 33072, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u0301-M.","family":"Garcia-Ferna\u0301ndez","sequence":"additional","affiliation":[{"name":"Departmento de Morfologia y Biologia Cellular, Universidad de Oviedo, Oviedo 33072, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell G.","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Biology, Sir Alexander Fleming Building, Imperial College of Science, Technology and Medicine, London, SW7 2AZ, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80464-X"},{"key":"e_1_3_1_3_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/27794","volume":"394","author":"Soni B. G.","year":"1998","unstructured":"Soni B. G., Philp A., Knox B. E., Foster R. G., Nature 394, 27 (1998).","journal-title":"Nature"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5393.1490"},{"key":"e_1_3_1_5_2","unstructured":"R. W. Rodieck The First Steps in Seeing (Sinauer Sunderland MA 1998)."},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.177.4048.532"},{"key":"e_1_3_1_7_2","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1073\/pnas.69.9.2547","volume":"69","author":"Deguchi T.","year":"1972","unstructured":"Deguchi T., Axelrod J., Proc. Natl. Acad. Sci. U.S.A. 69, 2547 (1972).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_1_8_2","unstructured":"___ ibid. p. 2208."},{"key":"e_1_3_1_9_2","unstructured":"J. Arendt Melatonin and the Mammalian Pineal Gland (Chapman & Hall Cambridge 1995)."},{"key":"e_1_3_1_10_2","unstructured":"R. J. Lucas and R. G. Foster Endocrinology in press."},{"key":"e_1_3_1_11_2","doi-asserted-by":"crossref","first-page":"8860","DOI":"10.1073\/pnas.94.16.8860","volume":"94","author":"Sun H.","year":"1997","unstructured":"Sun H., Macke J. P., Nathans J., Proc. Natl. Acad. Sci. U.S.A. 94, 8860 (1997).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_1_12_2","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/353655a0","volume":"353","author":"Jacobs G. H.","year":"1991","unstructured":"Jacobs G. H., Neitz J., Deegan J. F., Nature 353, 655 (1991).","journal-title":"Nature"},{"key":"e_1_3_1_13_2","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/0896-6273(92)90181-C","volume":"9","author":"Wang Y.","year":"1992","unstructured":"Wang Y., et al., Neuron 9, 429 (1992).","journal-title":"Neuron"},{"key":"e_1_3_1_14_2","unstructured":"The cl transgene was previously characterized in C57BL\/6 mice (12). However because this strain of mice does not produce pineal melatonin ["},{"key":"e_1_3_1_14_3","doi-asserted-by":"publisher","DOI":"10.1126\/science.3941912"},{"key":"e_1_3_1_14_4","unstructured":"] we introduced this transgene into the C3H\/He strain by at least nine generations of backcrossing."},{"key":"e_1_3_1_15_2","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0896-6273(00)80560-7","volume":"21","author":"Soucy E.","year":"1998","unstructured":"Soucy E., Wang Y., Nirenberg S., Nathans J., Meister M., Neuron 21, 481 (1998);","journal-title":"Neuron"},{"key":"e_1_3_1_15_3","unstructured":". Our reference to the cl transgene corresponds to the h.red DT-A construct in this paper."},{"key":"e_1_3_1_16_2","unstructured":"Total RNA was extracted from ( n = 4 to 6) eyes collected from 80-day-old wild-type cl and rd\/rd cl mice with the Promega (Southampton UK) SV RNA isolation kit. For Northern (RNA) blot analysis 5 \u03bcg of total RNA from each genotype was size-separated on a 1.2% agarose-formaldehyde electrophoresis gel and blotted overnight onto Hybond N+ membrane (Amersham). Three blots were hybridized with 32 P-labeled probes specific for mouse rod opsin [cDNA probe after"},{"key":"e_1_3_1_16_3","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0014-5793(88)80490-3","volume":"238","author":"Baehr W.","year":"1988","unstructured":"Baehr W., et al., FEBS Lett. 238, 253 (1988);","journal-title":"FEBS Lett."},{"key":"e_1_3_1_16_4","unstructured":"] and green and UV cone opsins [cRNA probes after"},{"key":"e_1_3_1_16_5","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0006-8993(97)00791-9","volume":"770","author":"von Schantz M.","year":"1997","unstructured":"von Schantz M., et al., Mol. Brain Res. 770, 131 (1997);","journal-title":"Mol. Brain Res."},{"key":"e_1_3_1_16_6","unstructured":"] and subsequently with a 32 P-labeled cDNA probe for glyceraldehyde phosphate dehydrogenase (GAPDH) (positive control). For reverse transcriptase\u2013polymerase chain reaction (RT-PCR) analysis cDNA was synthesized from 2 \u03bcg of total RNA from each genotype. PCR amplification was then undertaken over 35 cycles under optimized conditions with primers designed against the published sequences for mouse rod opsin green cone opsin UV cone opsin cone arrestin and tubulin (positive control). Appropriate negative controls (total RNA without reverse transcriptase step) were included for all genotypes. PCR reactions were separated on a 1.5% agarose gel and blotted overnight onto Hybond N+ membrane. Blots were hybridized with appropriate 32 P-labeled cDNA probes."},{"key":"e_1_3_1_17_2","unstructured":"Mice stably entrained to a 12 hour light:12 hour dark cycle were individually either sham-pulsed (no light exposure) or exposed to 15 min of defined irradiance (1.2 \u00d7 10 \u22124 1.2 \u00d7 10 \u22123 or 2.6 \u00d7 10 \u22122 \u03bcW\/ cm 2 ) with monochromatic light (\u03bb max = 509 nm half band width 10 nm) at zeitgeber time 20-21. The melatonin content of pineal homogenates was assessed by radioimmunoassay as described (9)."},{"key":"e_1_3_1_18_2","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/347677a0","volume":"347","author":"Bowes C.","year":"1990","unstructured":"Bowes C., et al., Nature 347, 677 (1990).","journal-title":"Nature"},{"key":"e_1_3_1_19_2","doi-asserted-by":"crossref","first-page":"8322","DOI":"10.1073\/pnas.88.19.8322","volume":"88","author":"Pittler S. J.","year":"1991","unstructured":"Pittler S. J., Baehr W., Proc. Natl. Acad. Sci. U.S.A. 88, 8322 (1991).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_1_20_2","first-page":"489","volume":"17","author":"Carter-Dawson L. D.","year":"1978","unstructured":"Carter-Dawson L. D., LaVail M. M., Sidman R. L., Investig. Ophthalmol. Vis. Sci. 17, 489 (1978).","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"e_1_3_1_21_2","unstructured":"We used polyclonal antisera (12) to the human blue cone pigment (used at 1:8000 dilution) and human red-green pigments (1:8000 dilution) and a monoclonal antibody to rat rod opsin ["},{"key":"e_1_3_1_21_3","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0014-4835(86)90017-5","volume":"42","author":"Hicks D.","year":"1986","unstructured":"Hicks D., Molday R. S., Exp. Eye Res. 42, 55 (1986);","journal-title":"Exp. Eye Res."},{"key":"e_1_3_1_21_4","unstructured":"; 1:20 000 dilution]."},{"key":"e_1_3_1_22_2","unstructured":"R. J. Lucas M. S. Freedman M. Mu\u00f1oz J.-M. Garcia-Fern\u00e1ndez R. G. Foster data not shown."},{"key":"e_1_3_1_23_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0006-8993(79)90848-5","volume":"174","author":"Klein D. C.","year":"1979","unstructured":"Klein D. C., Moore R. Y., Brain Res. 174, 245 (1979).","journal-title":"Brain Res."},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19980615)395:4<417::AID-CNE1>3.0.CO;2-4"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi962209o"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6097"},{"key":"e_1_3_1_27_2","unstructured":"I. Provencio G. Jiang W. J. DeGrip W. P. Hayes M. D. Rollag ibid. p. 340."},{"key":"e_1_3_1_28_2","unstructured":"L. Wetterberg Ed. Light and Biological Rhythms in Man (Pergamon Oxford 1993) vol. 62."},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5413.502"},{"key":"e_1_3_1_30_2","unstructured":"We thank J. Nathans and Y. Wang (Johns Hopkins University) for donation of the original C57BL\/6 cl mouse colony and the polyclonal antisera to cones and D. Hicks for the monoclonal antisera to rods. This work was supported by research grants from UK Biotechnology and Biological Sciences Research Council and European Union BioMed 2 program."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.284.5413.505","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T09:33:02Z","timestamp":1705138382000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.284.5413.505"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,4,16]]},"references-count":38,"journal-issue":{"issue":"5413","published-print":{"date-parts":[[1999,4,16]]}},"alternative-id":["10.1126\/science.284.5413.505"],"URL":"https:\/\/doi.org\/10.1126\/science.284.5413.505","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,4,16]]}}}