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Although\n                    <jats:italic>Sulf1<\/jats:italic>\n                    has established roles in development and cancer, its functions in the adult brain remain incompletely characterized. Recently we reported that\n                    <jats:italic>Sulf1<\/jats:italic>\n                    is expressed in the nucleus accumbens, overlapping with dopamine D1 and D2 receptors, and that\n                    <jats:italic>Sulf1<\/jats:italic>\n                    knockout (KO) mice showed altered reward and aversion learning. However, given that\n                    <jats:italic>Sulf1<\/jats:italic>\n                    is expressed in many other brain regions, including the prefrontal cortex, midline thalamic nuclei, etc.,\n                    <jats:italic>Sulf1<\/jats:italic>\n                    may have unknown brain functions. To explore the\n                    <jats:italic>Sulf1<\/jats:italic>\n                    functions across a broad range of contexts, we here perform a comprehensive behavioral analysis of male\n                    <jats:italic>Sulf1<\/jats:italic>\n                    KO mice, together with a re-analysis of the original data in which the false discovery rate (FDR) was controlled within defined groups of tests.\n                    <jats:italic>Sulf1<\/jats:italic>\n                    KO mice traveled less than wild-type (WT) mice in the open field test, and this reduction was reproduced in an independent cohort. Gait analysis on a treadmill revealed a redistribution of the forelimb stance phase, with a larger proportion spent braking and a smaller proportion spent propelling, together with an increased absolute paw angle; these forelimb changes were reproduced in 2 independent cohorts and at 2 treadmill speeds. Distance traveled was also reduced in a three-chamber apparatus and, before drug injection, at nominal significance in the home cage.\n                    <jats:italic>Sulf1<\/jats:italic>\n                    KO mice showed larger acoustic startle responses and reduced prepulse inhibition (PPI); the reduction in PPI was observed in all 5 drug-free or saline-treated sessions conducted in 2 independent cohorts and was also observed after haloperidol (0.3 or 1\u00a0mg\/kg) and, at nominal significance, after clozapine (3\u00a0mg\/kg) treatment. The locomotor, vertical, and stereotypic responses to methamphetamine were attenuated in\n                    <jats:italic>Sulf1<\/jats:italic>\n                    KO mice, with nominally significant drug \u00d7 genotype interactions. Increased baseline-subtracted contextual freezing provides a promising lead for further confirmation. Taken together, adult male\n                    <jats:italic>Sulf1<\/jats:italic>\n                    KO mice exhibit alterations in locomotor output, forelimb gait, and sensorimotor gating, implicating that\n                    <jats:italic>Sulf1<\/jats:italic>\n                    deficiency leads to a wide range of neurobehavioral abnormalities.\n                  <\/jats:p>","DOI":"10.1186\/s13041-026-01353-8","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:56:36Z","timestamp":1792266996000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive behavioral phenotyping of male Sulf1-deficient mice reveals reduced locomotor activity, altered forelimb gait, and reduced prepulse inhibition"],"prefix":"10.1186","volume":"19","author":[{"given":"Kazuko","family":"Keino-Masu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markos Michail","family":"Chatzigiannis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Shoji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Yamasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasue","family":"Horiuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadao","family":"Arinami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Hagino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutaka","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Miyakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Masu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,17]]},"reference":[{"issue":"2","key":"1353_CR1","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.jbiotec.2007.01.022","volume":"129","author":"WC Lamanna","year":"2007","unstructured":"Lamanna WC, Kalus I, Padva M, Baldwin RJ, Merry CL, Dierks T. 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No experiments reported in this article were performed at Fujita Health University. The human genetic association studies were approved by the ethics committees of the University of Tsukuba, Niigata University, Fujita Health University, Nagoya University, Okayama University and Seiwa Hospital (schizophrenia samples), and of the University of Tsukuba, RIKEN, Tokyo Medical and Dental University and the National Institute of Mental Health (mood disorder samples). Written informed consent was obtained from all participants.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"During the preparation of this manuscript, the authors used ChatGPT (OpenAI) and Claude (Anthropic) for language editing, for retrieval and tabulation of publicly available genome-wide association study summary statistics, for statistical computation and cross-checking of analyses performed on author-provided numerical data, and for the preparation of figures from those data. No artificial intelligence tool was used to generate or modify primary experimental data. All outputs were independently verified by the authors, who take full responsibility for the content of this article.","order":3,"name":"Ethics","label":"Use of AI and AI-assisted technologies","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"73"}}