{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:59:50Z","timestamp":1753891190758,"version":"3.41.2"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Fucosylation, a type of glycosylation, is the attachment of a fucose to <jats:italic>N<\/jats:italic>-glycans, <jats:italic>O<\/jats:italic>-glycans and glycolipids, and is critical for the post-translational regulation of many essential pathways. Here we describe a mouse strain with an <jats:italic>N<\/jats:italic>-ethyl-<jats:italic>N<\/jats:italic>-nitrosourea-induced point mutation in the gene encoding guanosine diphosphate (GDP)-mannose 4,6-dehydratase (GMDS), an enzyme involved in the generation of GDP-fucose, a substrate for fucosylation. <jats:italic>Gmds<jats:sup>Y187*\/Y187*<\/jats:sup><\/jats:italic> mice displayed growth retardation and increased postnatal mortality. Immunophenotyping of <jats:italic>Gmds<jats:sup>Y187*\/Y187*<\/jats:sup><\/jats:italic> mice revealed reduced numbers of double positive (DP), CD4 single positive (SP) and CD8SP T cells, despite normal numbers of double negative (DN) cells in the thymus of mutant animals. Similarly, analysis of the thymus in <jats:italic>Rag1<jats:sup>-\/-<\/jats:sup><\/jats:italic> mice reconstituted with <jats:italic>Gmds<jats:sup>Y187*\/Y187*<\/jats:sup><\/jats:italic> bone marrow cells revealed a partial arrest at the DN stage of T cell development compared to animals transplanted with <jats:italic>Gmds<jats:sup>+\/+<\/jats:sup><\/jats:italic> bone marrow cells. Furthermore, mixed chimeras showed that <jats:italic>Gmds<jats:sup>Y187*\/Y187*<\/jats:sup><\/jats:italic> T cells were unable to compete with <jats:italic>Gmds<jats:sup>+\/+<\/jats:sup><\/jats:italic> cells from the DP stage of T cell development in the thymus. This inability to compete resulted in the near absence of <jats:italic>Gmds<jats:sup>Y187*\/Y187*<\/jats:sup><\/jats:italic>-derived peripheral T cells in recipient mice, while B cell subsets were present at broadly normal frequencies. These findings provide the first evidence of an essential cell-intrinsic requirement for GMDS in early T cell development in mice.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1598923","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T05:29:37Z","timestamp":1750915777000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Essential cell-intrinsic requirement for GMDS in T cell development"],"prefix":"10.3389","volume":"16","author":[{"given":"Mehmet","family":"Yabas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla M.","family":"Roots","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. 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