{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:30:52Z","timestamp":1788348652428,"version":"build-2803163510"},"reference-count":30,"publisher":"American Society of Hematology","issue":"21","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,11,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Native circulating blood platelets present with a discoid flat morphology maintained by a submembranous peripheral ring of microtubules, named marginal band. The functional importance of this particular shape is still debated, but it was initially hypothesized to facilitate platelet interaction with the injured vessel wall and to contribute to hemostasis. The importance of the platelet discoid morphology has since been questioned on the absence of clear bleeding tendency in mice lacking the platelet-specific \u03b21-tubulin isotype, which exhibits platelets with a thinner marginal band and an ovoid shape. Here, we generated a mouse model inactivated for \u03b21-tubulin and \u03b14A-tubulin, an \u03b1-tubulin isotype strongly enriched in platelets. These mice present with fully spherical platelets completely devoid of a marginal band. In contrast to the single knockouts, the double deletion resulted in a severe bleeding defect in a tail-clipping assay, which was not corrected by increasing the platelet count to normal values by the thrombopoietin-analog romiplostim. In\u00a0vivo, thrombus formation was almost abolished in a ferric chloride\u2013injury model, with only a thin layer of loosely packed platelets, and mice were protected against death in a model of thromboembolism. In\u00a0vitro, platelets adhered less efficiently and formed smaller-sized and loosely assembled aggregates when perfused over von Willebrand factor and collagen matrices. In conclusion, this study shows that blood platelets require 2 unique \u03b1- and \u03b2-tubulin isotypes to acquire their characteristic discoid morphology. Lack of these 2 isotypes has a deleterious effect on flow-dependent aggregate formation and stability, leading to a severe bleeding disorder.<\/jats:p>","DOI":"10.1182\/blood.2022016729","type":"journal-article","created":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T19:03:02Z","timestamp":1661540582000},"page":"2290-2299","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":14,"title":["Loss of \u03b14A- and \u03b21-tubulins leads to severe platelet spherocytosis and strongly impairs hemostasis in mice"],"prefix":"10.1182","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1999-782X","authenticated-orcid":false,"given":"Quentin","family":"Kimmerlin","sequence":"first","affiliation":[{"name":"1Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Etablissement Fran\u00e7ais du Sang Grand Est, Unit\u00e9 Mixte de Recherche-S 1255, F\u00e9d\u00e9ration de M\u00e9decine Translationnelle de Strasbourg, Universit\u00e9 de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Moog","sequence":"additional","affiliation":[{"name":"1Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Etablissement Fran\u00e7ais du Sang Grand Est, Unit\u00e9 Mixte de Recherche-S 1255, F\u00e9d\u00e9ration de M\u00e9decine Translationnelle de Strasbourg, Universit\u00e9 de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5292-2312","authenticated-orcid":false,"given":"Alexandra","family":"Yakusheva","sequence":"additional","affiliation":[{"name":"1Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Etablissement Fran\u00e7ais du Sang Grand Est, Unit\u00e9 Mixte de Recherche-S 1255, F\u00e9d\u00e9ration de M\u00e9decine Translationnelle de Strasbourg, Universit\u00e9 de Strasbourg, Strasbourg, France"},{"name":"2Center for Theoretical Problems of Physicochemical Pharmacology, Cellular Hemostasis Lab, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Ziessel","sequence":"additional","affiliation":[{"name":"1Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Etablissement Fran\u00e7ais du Sang Grand Est, Unit\u00e9 Mixte de Recherche-S 1255, F\u00e9d\u00e9ration de M\u00e9decine Translationnelle de Strasbourg, Universit\u00e9 de Strasbourg, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9620-4961","authenticated-orcid":false,"given":"Anita","family":"Eckly","sequence":"additional","affiliation":[{"name":"1Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Etablissement Fran\u00e7ais du Sang Grand Est, Unit\u00e9 Mixte de Recherche-S 1255, F\u00e9d\u00e9ration de M\u00e9decine Translationnelle de Strasbourg, Universit\u00e9 de Strasbourg, Strasbourg, 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