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Challenges in studying TNF\u2010\u03b1 include its widespread gene expression, variability in expression levels, diverse protein forms, and low baseline expression, which complicate traditional detection and tracking methods. To address these challenges, we constructed three distinct transgenic luciferase reporter mouse models (TNF\u2010IRES\u2010Luc, TNF\u2010Nanoluc, and TNF\u2010HiBiT) driven by the endogenous TNF\u2010\u03b1 gene, using CRISPR\/Cas9 technology through homology\u2010directed repair. The firefly luciferase gene, secreted NanoLuc gene, and HiBiT gene were individually integrated into the mouse genome under the control of the endogenous TNF\u2010\u03b1 promoter. Our results demonstrate that endogenous TNF\u2010\u03b1 expression can be effectively monitored by measuring luciferase levels in vivo and in vitro, using an in vivo imaging system and a luminometer. This was validated during inflammatory processes such as lipopolysaccharide (LPS)\u2010induced sepsis and phorbol ester (TPA)\u2010induced mouse ear edema. Furthermore, the anti\u2010inflammatory drug dexamethasone (DXM) significantly inhibited TNF\u2010\u03b1 and luciferase expression in both inflammatory models. Our study demonstrates these mouse models are valuable tools for studying TNF\u2010\u03b1 expression in inflammatory responses and related diseases, as well as evaluating anti\u2010inflammatory drug efficacy.<\/jats:p>","DOI":"10.1002\/biot.70080","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T03:29:57Z","timestamp":1752722997000},"source":"Crossref","is-referenced-by-count":1,"title":["Establishment and Application of Mice Models for Tracing Gene Expression and Protein Product of TNF"],"prefix":"10.1002","volume":"20","author":[{"given":"Fangyang","family":"Shao","sequence":"first","affiliation":[{"name":"School of Life Sciences and Technology Tongji University  Shanghai China"},{"name":"Wenzhou Lucheng The Shaos Oral Clinic Ltd.  Wenzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1220-3859","authenticated-orcid":false,"given":"Yi","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Technology Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahao","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Technology Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Technology Tongji University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Technology Tongji University  Shanghai 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