{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:41:16Z","timestamp":1785796876591,"version":"3.56.0"},"reference-count":72,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Topoisomerase III\u03b2 (Top3\u03b2), the only dual-activity topoisomerase in mammals that can change topology of both DNA and RNA, is known to be associated with neurodevelopment and mental dysfunction in humans. However, there is no report showing clear associations of Top3\u03b2 with neuropsychiatric phenotypes in mice. Here, we investigated the effect of Top3\u03b2 on neuro-behavior using newly generated Top3\u03b2 deficient (Top3\u03b2\u2212\/\u2212) mice. We found that Top3\u03b2\u2212\/\u2212 mice showed decreased anxiety and depression-like behaviors. The lack of Top3\u03b2 was also associated with changes in circadian rhythm. In addition, a clear expression of Top3\u03b2 was demonstrated in the central nervous system of mice. Positron emission tomography\/computed tomography (PET\/CT) analysis revealed significantly altered connectivity between many brain regions in Top3\u03b2\u2212\/\u2212 mice, including the connectivity between the olfactory bulb and the cerebellum, the connectivity between the amygdala and the olfactory bulb, and the connectivity between the globus pallidus and the optic nerve. These connectivity alterations in brain regions are known to be linked to neurodevelopmental as well as psychiatric and behavioral disorders in humans. Therefore, we conclude that Top3\u03b2 is essential for normal brain function and behavior in mice and that Top3\u03b2 could be an interesting target to study neuropsychiatric disorders in humans.<\/jats:p>","DOI":"10.3390\/ijms222312806","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T22:01:11Z","timestamp":1638309671000},"page":"12806","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Topoisomerase III\u03b2 Deficiency Induces Neuro-Behavioral Changes and Brain Connectivity Alterations in Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Faiz Ur","family":"Rahman","sequence":"first","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeongudanji-ro 30, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You-Rim","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeongudanji-ro 30, Cheongju 28116, Korea"},{"name":"Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Chungdae-ro 1, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Kyeung","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeongudanji-ro 30, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae-rim","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeongudanji-ro 30, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Mi","family":"Cho","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeongudanji-ro 30, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeongudanji-ro 30, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Seoul National University Bundang Hospital, Gumi-ro 166, Seongnam 463-707, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimi","family":"Araki","sequence":"additional","affiliation":[{"name":"Institute of Resource Development and Analysis, Kumamoto University, Honjo 2-2-1, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-ichi","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Institute of Resource Development and Analysis, Kumamoto University, Honjo 2-2-1, Kumamoto 860-0811, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Ni","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeongudanji-ro 30, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seul Gi","family":"Park","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeongudanji-ro 30, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Kee","family":"Yoon","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeongudanji-ro 30, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kihoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeongudanji-ro 30, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Suk","family":"Won","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeongudanji-ro 30, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyoung-Chin","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeongudanji-ro 30, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younghee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Chungdae-ro 1, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6518-0602","authenticated-orcid":false,"given":"Ho-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Seoul National University Bundang Hospital, Gumi-ro 166, Seongnam 463-707, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki-Hoan","family":"Nam","sequence":"additional","affiliation":[{"name":"Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Yeongudanji-ro 30, Cheongju 28116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/nrm831","article-title":"Cellular roles of DNA topoisomerases: A molecular perspective","volume":"3","author":"Wang","year":"2002","journal-title":"Nat. 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