{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T14:16:38Z","timestamp":1772028998764,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T00:00:00Z","timestamp":1696291200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Restricted repetitive behaviors (RRBs), which are associated with many different neurological and mental disorders, such as obsessive\u2010compulsive disorder (OCD) and autism, are patterns of behavior with little variation and little obvious function. Paired Box 2 (<jats:italic>Pax2<\/jats:italic>) is a transcription factor that is expressed in many systems, including the kidney and the central nervous system. The protein that is encoded by <jats:italic>Pax2<\/jats:italic> has been implicated in the development of the nervous system and neurodevelopmental disorders. In our previous study, <jats:italic>Pax2<\/jats:italic> heterozygous gene knockout mice (<jats:italic>Pax2<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> mice) showed abnormally increased self\u2010grooming and impaired learning and memory abilities. However, it remains unclear which cell type is involved in this process. In this study, we deleted <jats:italic>Pax2<\/jats:italic> only in the nervous system to determine the regulatory mechanism of <jats:italic>Pax2<\/jats:italic> in RRBs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, <jats:italic>Pax2<\/jats:italic> nervous system\u2010specific knockout mice (<jats:italic>Nestin\u2010Pax2<\/jats:italic> mice<jats:italic>)<\/jats:italic> aged 6\u20138\u2009weeks and <jats:italic>Pax2<\/jats:italic> flox mice of the same age were recruited as the experimental group. Tamoxifen and vehicle were administered via intraperitoneal injection to induce <jats:italic>Pax2<\/jats:italic> knockout after gene identification. Western blotting was used to detect <jats:italic>Pax2<\/jats:italic> expression. After that, we assessed the general health of these two groups of mice. The self\u2010grooming test, marble burying test and T\u2010maze acquisition and reversal learning test were used to observe the lower\u2010order and higher\u2010order RRBs. The three\u2010chamber test, Y\u2010maze, and elevated plus\u2010maze were used to assess social ability, spatial memory ability, and anxiety. Neural circuitry tracing and transcriptome sequencing (RNA\u2010seq) were used to observe the abnormal neural circuitry, differentially expressed genes (DEGs) and signaling pathways affected by <jats:italic>Pax2<\/jats:italic> gene knockout in the nervous system and the putative molecular mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>(1) The <jats:italic>Nestin\u2010Pax2<\/jats:italic> mouse model was successfully constructed, and the <jats:italic>Nestin\u2010Pax2<\/jats:italic> mice showed decreased expression of <jats:italic>Pax2<\/jats:italic>. (2) <jats:italic>Nestin\u2010Pax2<\/jats:italic> mice showed increased self\u2010grooming behavior and impaired T\u2010maze reversal behavior compared with <jats:italic>Pax2<\/jats:italic> flox mice. (3) An increased number of projection fibers can be found in the mPFC projecting to the CA1 and BLA, and a reduction in IGFBP2 can be found in the hippocampus of <jats:italic>Nestin\u2010Pax2<\/jats:italic> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results demonstrated that loss of <jats:italic>Pax2<\/jats:italic> in the nervous system leads to restricted repetitive behaviors. The mechanism may be associated with impaired neural circuitry and a reduction in IGFBP2.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14482","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T08:19:20Z","timestamp":1696321160000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Impaired neural circuitry of hippocampus in <i>Pax2<\/i> nervous system\u2010specific knockout mice leads to restricted repetitive behaviors"],"prefix":"10.1111","volume":"30","author":[{"given":"Ying","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, Shanxi Provincial People's Hospital The Fifth Clinical Medical College of Shanxi Medical University  Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yizhuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanxi Provincial People's Hospital The Fifth 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