{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:04:35Z","timestamp":1789707875362,"version":"4.0.1"},"reference-count":32,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["1R15NS111401-01"],"award-info":[{"award-number":["1R15NS111401-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"award":["1R15NS111401-01"],"award-info":[{"award-number":["1R15NS111401-01"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"American Cancer Society","award":["#IRG-14-193-01"],"award-info":[{"award-number":["#IRG-14-193-01"]}],"id":[{"id":"https:\/\/ror.org\/02e463172","id-type":"ROR","asserted-by":"crossref"}]},{"award":["#IRG-14-193-01"],"award-info":[{"award-number":["#IRG-14-193-01"]}],"id":[{"id":"https:\/\/ror.org\/02e463172","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Augusta University","id":[{"id":"https:\/\/ror.org\/012mef835","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/012mef835","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tumor microenvironments (TME) play a crucial role in the formation, progression, and drug resistance of many cancers, including glioblastoma (GBM). Microglia are the resident innate immune cells of the central nervous system and are associated with brain cancers like GBM. However, there are limited studies about the specific effects that microglia have on GBM tumors. One possible way to reduce GBM tumor progression is by targeting key signaling pathways in microglia, such as the nuclear factor-kappa B (NF-\u03baB) signaling pathway, which has been implicated in both microglia\/macrophage phenotype polarization and in brain cancers like GBM. Therefore, this study aimed to produce a p65fl\/fl\/CX3CR1creER\/+ mouse model, an inducible p65 knockout mouse model to be used for studying how inhibition of canonical NF-\u03baB signaling in microglia affects GBM tumors. Following tamoxifen administration to the mouse, p65, a transcription factor of the canonical NF-\u03baB pathway, should be deleted in microglia due to activation of a Cre recombinase (creER) under the control of the CX3CR1 promoter. This mouse model was characterized to determine whether the p65 gene was effectively deleted in microglia using this system. Our data show that tamoxifen-treated p65fl\/fl\/CX3CR1creER\/+ mice had only partial deletion of the p65 gene, which corresponded to only slightly lower p65 expression in microglia compared to control mice. Partial p65 deletion in microglia was also observed in p65fl\/fl\/CX3CR1creER\/+ mice that received both GBM implantations and tamoxifen treatment compared to a vehicle control group. Despite the low p65 deletion efficiency, we show that slight decreases in microglial p65 can alter gene expression of various genes involved in microglial phenotype polarization, which is exacerbated in the context of GBM. Overall, the data from this study show minimal p65 deletion in microglia from tamoxifen-treated p65fl\/fl\/CX3CR1creER\/+ mice. The limitations of this model will serve as guidance to the GBM TME field for future animal model production.<\/jats:p>","DOI":"10.3390\/cells15181668","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:58:59Z","timestamp":1789545539000},"page":"1668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Challenges in Developing a Microglial NF-Kappa B Conditional Mouse Model for Glioblastoma Studies"],"prefix":"10.3390","volume":"15","author":[{"given":"Amy T.","family":"Trang","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7039-1911","authenticated-orcid":false,"given":"Ahmet","family":"Alptekin","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Goodall","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0017-5794","authenticated-orcid":false,"given":"Surendra K.","family":"Rajpurohit","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Frerichs","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1464-9823","authenticated-orcid":false,"given":"Thaiz F.","family":"Borin","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1842-1749","authenticated-orcid":false,"given":"Ahmet K.","family":"Korkaya","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karan","family":"Soni","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2902-3671","authenticated-orcid":false,"given":"Ali S.","family":"Arbab","sequence":"additional","affiliation":[{"name":"Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1337-8382","authenticated-orcid":false,"given":"Jennifer W.","family":"Bradford","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Soubannier, V., and Stifani, S. 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