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The robust nightly peak of melatonin secretion is an output signal of the circadian clock to the whole organism. However, so far the regulatory roles of endogenous melatonin in mammalian biological rhythms and physiology processes are poorly understood. Here, we establish congenic mouse lines (&gt;N10 generations) that are proficient or deficient in melatonin synthesis (AH+\/+ or AH\u2212\/\u2212 mice, respectively) on the C57BL\/6J genetic background by crossing melatonin\u2010proficient MSM\/Ms with C57BL\/6J. AH+\/+ mice displayed robust nightly peak of melatonin secretion and had significantly higher levels of pineal and plasma melatonin vs AH\u2212\/\u2212 mice. Using this mice model, we investigated the role of endogenous melatonin in regulating multiple biological rhythms, physiological processes, and rhythmic behaviors. In the melatonin\u2010proficient (AH+\/+) mice, the rate of re\u2010entrainment of wheel\u2010running activity was accelerated following a 6\u2010hour phase advance of dark onset when comparted with AH\u2212\/\u2212 mice, suggesting a role of endogenous melatonin in facilitating clock adjustment. Further in the AH+\/+ mice, there was a significant decrease in body weight, gonadal weight and reproductive performance, and a significant increase in daily torpor (a hypothermic and hypometabolic state lasting only hours during adverse conditions). Endogenous melatonin, however, had no effect in the modulation of the diurnal rhythm of 2\u2010[<jats:sup>125<\/jats:sup>I]\u2010iodomelatonin receptor expression in the SCN, free\u2010running wheel behavior in constant darkness, life span, spontaneous homecage behaviors, and various types of social\u2010emotional behaviors. The findings also shed light on the role of endogenous melatonin in mice domestication and provide new insights into melatonin's action in reducing energy expenditure during a food shortage. In summary, the congenic mice model generated in this study offers a significant advantage toward understanding of the role of endogenous melatonin in regulating melatonin receptor\u2010mediated rhythm behaviors and physiological functions.<\/jats:p>","DOI":"10.1111\/jpi.12748","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T08:16:45Z","timestamp":1622794605000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Impact of endogenous melatonin on rhythmic behaviors, reproduction, and survival revealed in melatonin\u2010proficient C57BL\/6J congenic mice"],"prefix":"10.1111","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7833-5172","authenticated-orcid":false,"given":"Chongyang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York (SUNY) Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon J.","family":"Clough","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York (SUNY) Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekue B.","family":"Adamah\u2010Biassi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York (SUNY) Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele H.","family":"Sveinsson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York (SUNY) Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York (SUNY) Buffalo NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuo","family":"Miura","sequence":"additional","affiliation":[{"name":"Technology and Development Team for Mouse Phenotype Analysis BioResource Research Center RIKEN Tsukuba\u2010shi Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamio","family":"Furuse","sequence":"additional","affiliation":[{"name":"Technology and Development Team for Mouse Phenotype Analysis BioResource Research Center RIKEN Tsukuba\u2010shi Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeharu","family":"Wakana","sequence":"additional","affiliation":[{"name":"Department of Gerontology Institute of Biomedical Research and Innovation Kobe\u2010shi Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yui K.","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Graduate School of Arts and Sciences The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Okanoya","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Graduate School of Arts and Sciences The University of Tokyo Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall L.","family":"Hudson","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Jacobs School of Medicine and Biomedical Sciences University at Buffalo, State University of New York (SUNY) Buffalo NY 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