{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:12:27Z","timestamp":1787015547494,"version":"build-2736575974"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T00:00:00Z","timestamp":1504137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","award":["NNF15OC0015988"],"award-info":[{"award-number":["NNF15OC0015988"]}],"id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002808","name":"Carlsbergfondet","doi-asserted-by":"publisher","award":["CF15\u20100515"],"award-info":[{"award-number":["CF15\u20100515"]}],"id":[{"id":"10.13039\/501100002808","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2017,10]]},"abstract":"Abstract<\/jats:title>\n \n The retinal and anterior neural fold homeobox gene\n (Rax)<\/jats:italic>\n controls development of the eye and the forebrain. Postnatal expression of\n Rax<\/jats:italic>\n in the brain is restricted to the pineal gland, a forebrain structure devoted to melatonin synthesis. The role of\n Rax<\/jats:italic>\n in pineal function is unknown. In order to investigate the role of\n Rax<\/jats:italic>\n in pineal function while circumventing forebrain abnormalities of the global\n Rax<\/jats:italic>\n knockout, we generated an eye and pineal\u2010specific\n Rax<\/jats:italic>\n conditional knockout mouse. Deletion of\n Rax<\/jats:italic>\n in the pineal gland did not affect morphology of the gland, suggesting that\n Rax<\/jats:italic>\n is not essential for pineal gland development. In contrast, deletion of\n Rax<\/jats:italic>\n in the eye generated an anophthalmic phenotype. In addition to the loss of central visual pathways, the suprachiasmatic nucleus of the hypothalamus housing the circadian clock was absent, indicating that the retinohypothalamic tract is required for the nucleus to develop. Telemetric analyses confirmed the lack of a functional circadian clock. Arylalkylamine N\u2010acetyltransferase (\n Aanat<\/jats:italic>\n ) transcripts\n ,<\/jats:italic>\n encoding the melatonin rhythm\u2010generating enzyme, were undetectable in the pineal gland of the\n Rax<\/jats:italic>\n conditional knockout under normal conditions, whereas the paired box 6 homeobox gene, known to regulate pineal development, was up\u2010regulated. By injecting isoproterenol, which mimics a nocturnal situation in the pineal gland, we were able to induce pineal expression of\n Aanat<\/jats:italic>\n in the\n Rax<\/jats:italic>\n conditional knockout mouse, but\n Aanat<\/jats:italic>\n transcript levels were significantly lower than those of\n Rax<\/jats:italic>\n \u2010proficient mice. Our data suggest that\n Rax<\/jats:italic>\n controls pineal gene expression and via\n Aanat<\/jats:italic>\n may modulate melatonin synthesis.\n <\/jats:p>","DOI":"10.1111\/jnc.14120","type":"journal-article","created":{"date-parts":[[2017,7,4]],"date-time":"2017-07-04T09:59:43Z","timestamp":1499162383000},"page":"100-111","source":"Crossref","is-referenced-by-count":13,"title":["A modulatory role of the\n Rax<\/i>\n homeobox gene in mature pineal gland function: Investigating the photoneuroendocrine circadian system of a\n Rax<\/i>\n conditional knockout mouse"],"prefix":"10.1111","volume":"143","author":[{"given":"Kristian","family":"Rohde","sequence":"first","affiliation":[{"name":"Department of Neuroscience Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tenna","family":"Bering","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"},{"name":"Laboratory of Neuropsychiatry Psychiatric Center Copenhagen Mental Health Services of the Capital Region of Denmark Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Laboratory for Molecular and Developmental Biology Institute for Protein Research Osaka University Suita Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4047-6324","authenticated-orcid":false,"given":"Martin Fredensborg","family":"Rath","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Faculty of Health and Medical Sciences University of Copenhagen Copenhagen 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