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In particular, the SNP rs2230912, which results in a glutamine-to-arginine substitution at position 460, has repeatedly been associated with mood disorders. Although this SNP per se does not affect receptor function, it tags a gain-of-function haplotype that has been shown to significantly enhance receptor activity. BAC-transgenic P2X7-reporter mice have proven to be valuable tools for monitoring P2X7 expression. Here, we exploited their capacity to simultaneously overexpress the receptor, thereby serving as gain-of-function models to assess the behavioral consequences of elevated P2X7 levels. We used the two currently available transgenic P2X7 reporter lines (sEGFP and P2X7-EGFP), which differ in their expression pattern, degree of overexpression, and co-expression of the neighbouring\n                    <jats:italic>P2rx4<\/jats:italic>\n                    gene. Male sEGFP and P2X7-EGFP mice showed no alterations in general activity or in measures of anxiety-related or stress-coping behavior compared to their wild-type littermates. Only male P2X7-EGFP mice exhibited slightly delayed locomotor habituation to a novel environment. To what extent higher expression levels reflect enhanced receptor activity, as conveyed by the disease-associated gain-of-function haplotype, requires further investigation. Overall, these results indicate that P2X7 overexpression\u2014whether at endogenous or ectopic sites, or in conjunction with P2X4\u2014is not sufficient to substantially alter behavior of individually housed male mice under baseline conditions.\n                  <\/jats:p>","DOI":"10.1007\/s11302-026-10157-3","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T09:03:39Z","timestamp":1778317419000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased P2X7 level does not affect anxiety or stress-coping behavior in male mice"],"prefix":"10.1007","volume":"22","author":[{"given":"Lidia","family":"Urbina-Trevi\u00f1o","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iven-Alex","family":"von M\u00fccke-Heim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Engel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Nicke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M.","family":"Deussing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"10157_CR1","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.bcp.2017.12.021","volume":"151","author":"E Adinolfi","year":"2018","unstructured":"Adinolfi E et al (2018) The P2X7 receptor: a main player in inflammation. 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All experiments were performed in accordance with the European Communities\u2019 Council Directive 2010\/63\/EU and with the ARRIVE 2.0 guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Lidia Urbina-Trevi\u00f1o declares no conflicts of interest. Tang Hao declares no conflicts of interest Iven-Alex von M\u00fccke-Heim. Tobias Engel declares no conflicts of interest. Annette Nicke declares no conflicts of interest. Jan M Deussing declares no conflicts of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}],"article-number":"45"}}