{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:46:33Z","timestamp":1781106393293,"version":"3.54.1"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,1,21]]},"abstract":"<jats:p>\n                    Bruton tyrosine kinase (Btk) is essential for the development of pre-B cells to mature B cell stages.\n                    <jats:italic>Btk<\/jats:italic>\n                    -deficient mice manifest an X-linked immunodeficiency (\n                    <jats:italic>xid<\/jats:italic>\n                    ) defect characterized by a reduction of peripheral IgM\n                    <jats:sup>low<\/jats:sup>\n                    IgD\n                    <jats:sup>high<\/jats:sup>\n                    B cells, a lack of peritoneal CD5\n                    <jats:sup>+<\/jats:sup>\n                    B cells, low serum levels of IgM and IgG3, and impaired responses to T cell independent type II (TI-II) antigens. We have generated transgenic mice in which expression of the human\n                    <jats:italic>Btk<\/jats:italic>\n                    gene is driven by the murine class II major histocompatibility complex Ea gene locus control region, which provides gene expression from the pre-B cell stage onwards. When these transgenic mice were mated onto a\n                    <jats:italic>Btk<\/jats:italic>\n                    <jats:sup>\u2212<\/jats:sup>\n                    background, correction of the\n                    <jats:italic>xid<\/jats:italic>\n                    B cell defects was observed: B cells differentiated to mature IgM\n                    <jats:sup>low<\/jats:sup>\n                    IgD\n                    <jats:sup>high<\/jats:sup>\n                    stages, peritoneal CD5\n                    <jats:sup>+<\/jats:sup>\n                    B cells were present, and serum Ig levels and\n                    <jats:italic>in vivo<\/jats:italic>\n                    responses to TI-II antigens were in the normal ranges. A comparable rescue by transgenic\n                    <jats:italic>Btk<\/jats:italic>\n                    expression was also observed in heterozygous\n                    <jats:italic>Btk<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    female mice in those B-lineage cells that were\n                    <jats:italic>Btk<\/jats:italic>\n                    -deficient as a result of X chromosome inactivation. These findings indicate that the\n                    <jats:italic>Btk<\/jats:italic>\n                    <jats:sup>\u2212<\/jats:sup>\n                    phenotype in the mouse can be corrected by expression of human\n                    <jats:italic>Btk<\/jats:italic>\n                    from the pre-B cell stage onwards.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.2.610","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:43:20Z","timestamp":1027680200000},"page":"610-615","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":30,"title":["Correction of the X-linked immunodeficiency phenotype by transgenic expression of human Bruton tyrosine kinase under the control of the class II major histocompatibility complex Ea locus control\u2009region"],"prefix":"10.1073","volume":"94","author":[{"given":"Dubravka","family":"Drabek","sequence":"first","affiliation":[{"name":"Departments of Cell Biology and Genetics and Immunology, Faculty of Medicine, Dr Molewaterplein 50, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Experimental Pathology, University Medical and Dental School, Guy\u2019s Hospital, London SE1 9RT, United Kingdom; and Department of Immunohaematology, University Hospital Leiden, Rijnsburgerweg 10, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selina","family":"Raguz","sequence":"additional","affiliation":[{"name":"Departments of Cell Biology and Genetics and Immunology, Faculty of Medicine, Dr Molewaterplein 50, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Experimental Pathology, University Medical and Dental School, Guy\u2019s Hospital, London SE1 9RT, United Kingdom; and Department of Immunohaematology, University Hospital Leiden, Rijnsburgerweg 10, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton\u2009P.\u2009M.","family":"De Wit","sequence":"additional","affiliation":[{"name":"Departments of Cell Biology and Genetics and Immunology, Faculty of Medicine, Dr Molewaterplein 50, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Experimental Pathology, University Medical and Dental School, Guy\u2019s Hospital, London SE1 9RT, United Kingdom; and Department of Immunohaematology, University Hospital Leiden, Rijnsburgerweg 10, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma\u2009M.","family":"Dingjan","sequence":"additional","affiliation":[{"name":"Departments of Cell Biology and Genetics and Immunology, Faculty of Medicine, Dr Molewaterplein 50, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Experimental Pathology, University Medical and Dental School, Guy\u2019s Hospital, London SE1 9RT, United Kingdom; and Department of Immunohaematology, University Hospital Leiden, Rijnsburgerweg 10, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huub\u2009F.\u2009J.","family":"Savelkoul","sequence":"additional","affiliation":[{"name":"Departments of Cell Biology and Genetics and Immunology, Faculty of Medicine, Dr Molewaterplein 50, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Experimental Pathology, University Medical and Dental School, Guy\u2019s Hospital, London SE1 9RT, United Kingdom; and Department of Immunohaematology, University Hospital Leiden, Rijnsburgerweg 10, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Grosveld","sequence":"additional","affiliation":[{"name":"Departments of Cell Biology and Genetics and Immunology, Faculty of Medicine, Dr Molewaterplein 50, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Experimental Pathology, University Medical and Dental School, Guy\u2019s Hospital, London SE1 9RT, United Kingdom; and Department of Immunohaematology, University Hospital Leiden, Rijnsburgerweg 10, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf\u2009W.","family":"Hendriks","sequence":"additional","affiliation":[{"name":"Departments of Cell Biology and Genetics and Immunology, Faculty of Medicine, Dr Molewaterplein 50, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands; Department of Experimental Pathology, University Medical and Dental School, Guy\u2019s Hospital, London SE1 9RT, United Kingdom; and Department of Immunohaematology, University Hospital Leiden, Rijnsburgerweg 10, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1997,1,21]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/361226a0"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90667-F"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2443.1996.d01-234.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/24.1.160"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950181009"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1994.tb00844.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1994.tb00849.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60631-8"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60834-2"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8332901"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8332900"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90114-0"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00867.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/297589a0"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/306270a0"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)51014-6"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.20.9524"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.22.10606"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.6.2101"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.3.627.bloodjournal853627"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198608283150907"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.165.4.949"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.158.3.920"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830231210"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/21.9.2065"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1994.tb03425.x"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.10.040192.000305"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.5.1213"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.4049\/jimmunol.133.4.1710","volume":"133","author":"Gerdes 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