{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T09:12:08Z","timestamp":1772269928307,"version":"3.50.1"},"reference-count":40,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T00:00:00Z","timestamp":1547596800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad of Spain","doi-asserted-by":"crossref","award":["ICOOPB20224"],"award-info":[{"award-number":["ICOOPB20224"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Spanish Research Council"},{"name":"CONACYT"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Wiskott-Aldrich syndrome (WAS) is a recessive X-linked inmmunodeficiency caused by loss-of-function mutations in the gene encoding the WAS protein (WASp). WASp plays an important role in the polymerization of the actin cytoskeleton in hematopoietic cells through activation of the Arp2\/3 complex. In a previous study, we found that actin cytoskeleton proteins, including WASp, were silenced in murine erythroleukemia cells defective in differentiation. Here, we designed a CRISPR\/Cas9 strategy to delete a 9.5-kb genomic region encompassing the\n                    <jats:italic>Was<\/jats:italic>\n                    gene in the X chromosome of murine erythroleukemia (MEL) cells. We show that\n                    <jats:italic>Was<\/jats:italic>\n                    -deficient MEL cells have a poor organization of the actin cytoskeleton that can be recovered by restoring\n                    <jats:italic>Was<\/jats:italic>\n                    expression. We found that whereas the total amount of actin protein was similar between wild-type and\n                    <jats:italic>Was<\/jats:italic>\n                    knockout MEL cells, the latter exhibited an altered ratio of monomeric G-actin to polymeric F-actin. We also demonstrate that\n                    <jats:italic>Was<\/jats:italic>\n                    overexpression can mediate the activation of Bruton\u2019s tyrosine kinase. Overall, these findings support the role of WASp as a key regulator of F-actin in erythroid cells.\n                  <\/jats:p>","DOI":"10.7717\/peerj.6284","type":"journal-article","created":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T04:04:45Z","timestamp":1547611485000},"page":"e6284","source":"Crossref","is-referenced-by-count":2,"title":["CRISPR\/Cas9-mediated deletion of the Wiskott-Aldrich syndrome locus causes actin cytoskeleton disorganization in murine erythroleukemia cells"],"prefix":"10.7717","volume":"7","author":[{"given":"Vanessa","family":"Fern\u00e1ndez-Calleja","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Biology, Centro de Investigaciones Biol\u00f3gicas, Spanish National Research Council (CSIC), Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda-Jos\u00e9","family":"Fern\u00e1ndez-Nestosa","sequence":"additional","affiliation":[{"name":"Bioinformatic Laboratory, Polytechnic School, National University of Asuncion, San Lorenzo, Paraguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, Centro de Investigaciones Biol\u00f3gicas, Spanish National Research Council (CSIC), Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge B.","family":"Schvartzman","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, Centro de Investigaciones Biol\u00f3gicas, Spanish National Research Council (CSIC), Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dora B.","family":"Krimer","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology, Centro de Investigaciones Biol\u00f3gicas, Spanish National Research Council (CSIC), Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2019,1,16]]},"reference":[{"key":"10.7717\/peerj.6284\/ref-1","doi-asserted-by":"publisher","first-page":"3231","DOI":"10.1182\/blood-2009-09-239087","article-title":"X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options","volume":"115","author":"Albert","year":"2010","journal-title":"Blood"},{"key":"10.7717\/peerj.6284\/ref-2","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1242\/jcs.199570","article-title":"Cellular functions of WASP family proteins at a glance","volume":"130","author":"Alekhina","year":"2017","journal-title":"Journal of Cell Science"},{"key":"10.7717\/peerj.6284\/ref-3","doi-asserted-by":"publisher","first-page":"4654","DOI":"10.1073\/pnas.080074897","article-title":"Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 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