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Here we describ the generation of two yeast artificial chromosome (YAC)\u2010transgenic mouse strains in which high\u2010level expression of human <jats:italic>Btk<\/jats:italic> is provided by endogenous regulatory cis\u2010acting elements that are present on a 340\u2010kb transgene, Yc340\u2010h<jats:italic>Btk.<\/jats:italic> The expression pattern of the transgenic human <jats:italic>Btk<\/jats:italic> was found to parallel that of the endogenous murine gene. When the Yc340\u2010h<jats:italic>Btk<\/jats:italic>\u2010transgenic mice were mated onto a <jats:italic>Btk<\/jats:italic>\u2010deficient background, the <jats:italic>xid<\/jats:italic> B cell defects were fully corrected: conventional and CD5<jats:sup>+<\/jats:sup> B\u20101 B cells were present in normal numbers, serum IgM and IgG3 levels as well as responses to T cell\u2010independent type II antigens were in the normal ranges. <jats:italic>In vivo<\/jats:italic> competition experiments in <jats:italic>Btk<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> female mice demonstrated that in the conventional B cell population the Yc340\u2010h<jats:italic>Btk<\/jats:italic> transgene could fully compensate the absence of expression of endogenous murine <jats:italic>Btk.<\/jats:italic> We conclude that in the YAC\u2010transgenic mice <jats:italic>Btk<\/jats:italic> is appropriately expressed in the context of native regulatory sequences.<\/jats:p>","DOI":"10.1002\/eji.1830270910","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T05:33:26Z","timestamp":1172813606000},"page":"2180-2187","source":"Crossref","is-referenced-by-count":21,"title":["The X\u2010linked immunodeficiency defect in the mouse is corrected by expression of human <i>Bruton's tyrosine kinase<\/i> from a yeast artificial chromosome transgene"],"prefix":"10.1002","volume":"27","author":[{"given":"Alex","family":"Maas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gemma M.","family":"Dingjan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huub F. 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