{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:31:36Z","timestamp":1790289096565,"version":"4.1.0"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"39","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,9,25]]},"abstract":"<jats:p>\n                    Although T cell dysfunction and lymphopenia are key features of immunodeficient patients with the Wiskott\u2013Aldrich syndrome and Wiskott\u2013Aldrich syndrome protein (WASP)-deficient mice, T cell development appears relatively normal. We hypothesized that N-WASP, a ubiquitously expressed homologue of WASP, may serve a redundant function with WASP. To examine the unique and redundant activities of WASP and N-WASP, we generated ES cells devoid of WASP and N-WASP [double knockout (DKO)] and used the RAG-2-deficient blastocyst complementation system to generate DKO lymphocytes. Moreover, we mated WASP KO mice with mice containing a conditionally targeted N-WASP allele and used the Cre-loxP system to generate mice lacking WASP and N-WASP in T cells [conditional DKO (cDKO)]. In both systems, N-WASP-deficient cells were indistinguishable from WT cells. In contrast, T cell development in DKO and cDKO mice was markedly altered, as shown by thymic hypocellularity and reduced numbers of peripheral T cells. We found that the combined activity of WASP and N-WASP was important for CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>\u2212<\/jats:sup>\n                    double-negative (DN)-to-CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    double-positive (DP) cell transition, and this may be partly explained by reduced cycling DN3 cells. In addition, decreased migratory responses of CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>\u2212<\/jats:sup>\n                    and CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    single-positive (SP) cells and increased percentage of CD69\n                    <jats:sup>low<\/jats:sup>\n                    CD24\n                    <jats:sup>low<\/jats:sup>\n                    and CD62L\n                    <jats:sup>low<\/jats:sup>\n                    SP cells in cDKO cells imply retention of SP cells in the thymus. In summary, this study suggests that, although WASP serves a unique role for peripheral T cell function, T cell development depends on the combined activity of WASP and N-WASP.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0706881104","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T21:04:45Z","timestamp":1190149485000},"page":"15424-15429","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":98,"title":["Wiskott\u2013Aldrich syndrome protein (WASP) and N-WASP are critical for T cell development"],"prefix":"10.1073","volume":"104","author":[{"given":"Vinicius","family":"Cotta-de-Almeida","sequence":"first","affiliation":[{"name":"*Gastrointestinal Unit,"},{"name":"Center for the Study of Inflammatory Bowel Disease,"},{"name":"Medicine, Harvard Medical School, Boston, MA 02115; and"},{"name":"Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, RJ, 21045-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Westerberg","sequence":"additional","affiliation":[{"name":"*Gastrointestinal Unit,"},{"name":"Center for the Study of Inflammatory Bowel Disease,"},{"name":"Medicine, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel H.","family":"Maillard","sequence":"additional","affiliation":[{"name":"*Gastrointestinal Unit,"},{"name":"Center for the Study of Inflammatory Bowel Disease,"},{"name":"Medicine, Harvard Medical School, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilek","family":"Onaldi","sequence":"additional","affiliation":[{"name":"*Gastrointestinal Unit,"},{"name":"Center for the Study of Inflammatory Bowel Disease,"},{"name":"Medicine, Harvard Medical School, Boston, MA 02115; 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