{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T16:25:11Z","timestamp":1788020711931,"version":"build-2784847793"},"reference-count":55,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-15-00035"],"award-info":[{"award-number":["21-15-00035"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Tryptophan hydroxylase 2 (TPH2) is the key and rate-limited enzyme of serotonin (5-HT) synthesis in the brain. The C1473G mutation in the Tph2 gene results in a two-fold decrease in enzyme activity in the mouse brain. The lethal yellow (AY) mutation in the Raly-Agouti locus results in the overexpression of the Agouti gene in the brain and causes obesity and depressive-like behavior in mice. Herein, the possible influences of these mutations and their combination on body mass, behavior, brain 5-HT and melanocortin systems in mice of the B6-1473CC\/aa. B6-1473CC\/AYa, B6-1473GG\/aa are investigated. B6-1473GG\/AYa genotypes were studied. The 1473G and AY alleles increase the activity of TPH2 and the expression of the Agouti gene, respectively, but they do not alter 5-HT and 5-HIAA levels or the expression of the genes Tph2, Maoa, Slc6a4, Htr1a, Htr2a, Mc3r and Mc4r in the brain. The 1473G allele attenuates weight gain and depressive-like immobility in the forced swim test, while the AY allele increases body weight gain and depressive-like immobility. The combination of these alleles results in hind limb dystonia in the B6-1473GG\/AYa mice. This is the first evidence for the interaction between the C1473G and AY mutations.<\/jats:p>","DOI":"10.3390\/biom13060963","type":"journal-article","created":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T03:59:56Z","timestamp":1686196796000},"page":"963","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effects of the Combination of the C1473G Mutation in the Tph2 Gene and Lethal Yellow Mutations in the Raly-Agouti Locus on Behavior, Brain 5-HT and Melanocortin Systems in Mice"],"prefix":"10.3390","volume":"13","author":[{"given":"Polyna D.","family":"Komleva","sequence":"first","affiliation":[{"name":"Department of Psychoneuropharmacology, Federal Research Center Institute of Cytology and Genetic Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9491-5782","authenticated-orcid":false,"given":"Ghofran","family":"Alhalabi","sequence":"additional","affiliation":[{"name":"Department of Genetic Collections of Neural Disorders, Federal Research Center Institute of Cytology and Genetic Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arseniy E.","family":"Izyurov","sequence":"additional","affiliation":[{"name":"Department of Genetics of Industrial Microorganisms, Federal Research Center Institute of Cytology and Genetic Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita V.","family":"Khotskin","sequence":"additional","affiliation":[{"name":"Department of Genetic Collections of Neural Disorders, Federal Research Center Institute of Cytology and Genetic Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3816-6244","authenticated-orcid":false,"given":"Alexander V.","family":"Kulikov","sequence":"additional","affiliation":[{"name":"Department of Genetic Collections of Neural Disorders, Federal Research Center Institute of Cytology and Genetic Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1126\/science.1078197","article-title":"Synthesis of serotonin by a second tryptophan hydroxylase isoform","volume":"299","author":"Walther","year":"2003","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1016\/S0006-2952(03)00556-2","article-title":"A unique central tryptophan hydroxylase isoform","volume":"66","author":"Walther","year":"2003","journal-title":"Biochem. 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