{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:34:36Z","timestamp":1791232476740,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Jerome LeJeune Foundation and Smith-Magenis syndrome Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Haploinsufficiency of retinoic acid-induced 1 (RAI1) is responsible for Smith\u2013Magenis syndrome (SMS), a childhood neurodevelopmental disorder associated with hyperphagia, obesity and autistic features. We previously showed that constitutive inactivation of one or both copies of Rai1 in the germline or developing brain induces SMS-like neurobehavioral deficits and obesity in mice. By contrast, the postnatal function of Rai1 is unclear. Here, we globally deleted one or both copies of Rai1 during two postnatal developmental windows by generating an inducible Rai1 knockout mouse model. We found that delayed Rai1 deletion at 3 or 8\u00a0weeks of age had no effect on neurobehavioral functions but resulted in adult-onset obesity and decreased expression of brain-derived neurotrophic factor (Bdnf) in the hypothalamus. Remarkably, genetic overexpression of human Bdnf in Rai1 heterozygous mice reversed SMS-like obesity, hyperphagia, metabolic syndrome-like features and hyposociability. Increasing Bdnf signaling in the paraventricular nucleus of the hypothalamus or the ventromedial nucleus of the hypothalamus was sufficient to mediate the anti-obesity effect. Our work identifies the function of Rai1 in different temporal windows after birth and provides in vivo evidence that increasing Bdnf signaling is therapeutically effective in a preclinical mouse model of SMS.<\/jats:p>","DOI":"10.1093\/hmg\/ddab245","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T12:41:59Z","timestamp":1630413719000},"page":"275-288","source":"Crossref","is-referenced-by-count":26,"title":["Temporal dissection of Rai1 function reveals brain-derived neurotrophic factor as a potential therapeutic target for Smith\u2013Magenis syndrome"],"prefix":"10.1093","volume":"31","author":[{"given":"Sehrish","family":"Javed","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurosurgery, Centre for Research in Neuroscience, McGill University, Montr\u00e9al, QC H3G 1A3, Canada"},{"name":"Brain Repair and Integrative Neuroscience Program, The Research Institute of the McGill University Health Centre, Montr\u00e9al, QC H3G 1A3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Centre for Research in Neuroscience, McGill University, Montr\u00e9al, QC H3G 1A3, Canada"},{"name":"Brain Repair and Integrative Neuroscience Program, The Research Institute of the McGill University Health Centre, Montr\u00e9al, QC H3G 1A3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Hsiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Centre for Research in Neuroscience, McGill University, Montr\u00e9al, QC H3G 1A3, Canada"},{"name":"Brain Repair and Integrative Neuroscience Program, The Research Institute of the McGill University Health Centre, Montr\u00e9al, QC H3G 1A3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"2022010913473871300_ref1","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/ng1126","article-title":"Mutations in RAI1 associated with Smith-Magenis syndrome","volume":"33","author":"Slager","year":"2003","journal-title":"Nat. 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