{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T07:53:59Z","timestamp":1770969239904,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,4,24]],"date-time":"2006-04-24T00:00:00Z","timestamp":1145836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Murine models of <jats:italic>\u03b2<\/jats:italic>\u2010thalassaemia have been used to test therapeutic globin gene vectors. However, the level of <jats:italic>\u03b3<\/jats:italic>\u2010globin expression necessary to achieve full phenotypic correction in these models is unclear. In order to address this issue, we carried out breeding and transplantation studies in murine models of <jats:italic>\u03b2<\/jats:italic>\u2010thalassaemia intermedia (<jats:italic>Hbb<\/jats:italic><jats:sup><jats:italic>th<\/jats:italic>\u22123<\/jats:sup>\/+) and severe <jats:italic>\u03b2<\/jats:italic>\u2010thalassaemia major (<jats:italic>Hbb<\/jats:italic><jats:sup><jats:italic>th<\/jats:italic>\u22123<\/jats:sup>\/<jats:italic>Hbb<\/jats:italic><jats:sup><jats:italic>th<\/jats:italic>\u22123<\/jats:sup>) using transgenic lines expressing various levels of human <jats:italic>\u03b3<\/jats:italic>\u2010globin. Expression of <jats:italic>\u03b3<\/jats:italic>\u2010globin RNA at a modest 7\u201314% of total <jats:italic>\u03b1<\/jats:italic>\u2010globin RNA resulted in the selective survival of HbF(+) erythrocytes, a fivefold increase in total HbF, and a phenotypic improvement in the <jats:italic>\u03b2<\/jats:italic>\u2010thalassaemia intermedia model. Full normalisation of erythrocyte indices in this model required <jats:italic>\u03b3<\/jats:italic>\u2010globin RNA expression at 27% of <jats:italic>\u03b1<\/jats:italic>\u2010globin, resulting in an average 40% (6\u00b78\u2003g\/dl) HbF. Studies using the homozygous <jats:italic>Hbb<\/jats:italic><jats:sup><jats:italic>th<\/jats:italic>\u22123<\/jats:sup> model of lethal <jats:italic>\u03b2<\/jats:italic>\u2010thalassaemia major demonstrated that even this high level of <jats:italic>\u03b3<\/jats:italic>\u2010globin expression, for reasons related to the function of the hybrid globin tetramers, could only prolong, but not fully support, survival. Taken together, these results indicate that only the heterozygous <jats:italic>Hbb<\/jats:italic><jats:sup><jats:italic>th<\/jats:italic>\u22123<\/jats:sup> model of <jats:italic>\u03b2<\/jats:italic>\u2010thalassaemia intermedia can be reliably used for the pre\u2010clinical assessment of <jats:italic>\u03b3<\/jats:italic>\u2010globin gene therapy vectors, as well as other means of <jats:italic>\u03b3<\/jats:italic>\u2010globin gene induction.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2006.06102.x","type":"journal-article","created":{"date-parts":[[2006,4,24]],"date-time":"2006-04-24T08:40:05Z","timestamp":1145868005000},"page":"100-108","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effects of human <i>\u03b3<\/i>\u2010globin in murine <i>\u03b2<\/i>\u2010thalassaemia"],"prefix":"10.1111","volume":"134","author":[{"given":"Tamon","family":"Nishino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Stamatoyannopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Emery","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,5,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-04-1522"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.17.4.2076"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1976.tb03599.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1182\/blood.V77.6.1326.1326","article-title":"Locus control region \u2013 a gamma transgenic mice: a new model for studying the induction of fetal hemoglobin in the adult","volume":"77","author":"Constantoulakis P.","year":"1991","journal-title":"Blood"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.990220107"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0219"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.18.7033"},{"key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1182\/blood.V24.3.223.223","article-title":"Hereditary persistence of fetal hemoglobin in Greece. 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