{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T20:55:49Z","timestamp":1785531349226,"version":"3.56.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We previously demonstrated that IL-3 stimulates transcription of the antiapoptotic gene mcl-1 via two promoter elements designated as the SIE and CRE-2 sites. To further study the functional role of these two DNA elements, mutant mice with targeted mutations of both SIE and CRE-2 sites (SC mutants) were generated. Homozygous SC mutants manifested a markedly reduced level of Mcl-1 in thymus but not in other major organs such as spleen, liver, lung, or heart. Reduced expression of Mcl-1 in SC mutant thymus resulted in attenuated positive selection of double-positive thymocytes into both CD4 and CD8 lineages, a result likely due to reduced survival of SC mutant double-positive thymocytes that were supposed to be positively selected. In contrast, in the peripheral lymphoid organs, only CD8+ but not CD4+ T cells were significantly reduced in homozygous SC mutant mice, a result consistent with a more dramatic decrease both of Mcl-1 expression and cell viability in mutant CD8+ compared with mutant CD4+ T cells. Impaired T cell development and peripheral CD8+ lymphopenia in homozygous SC mutant mice were both cell autonomous and could be rescued by enforced expression of human Mcl-1. Together, the promoter-knock-in mouse model generated in this study not only revealed a role of Mcl-1 in thymocyte-positive selection, but also uncovered that Mcl-1 expression is regulated in a tissue or cell lineage-specific manner.<\/jats:p>","DOI":"10.4049\/jimmunol.0803550","type":"journal-article","created":{"date-parts":[[2009,2,20]],"date-time":"2009-02-20T17:41:32Z","timestamp":1235151692000},"page":"2959-2968","source":"Crossref","is-referenced-by-count":11,"title":["Promoter Knock-In Mutations Reveal a Role of Mcl-1 in Thymocyte-Positive Selection and Tissue or Cell Lineage-Specific Regulation of Mcl-1 Expression"],"prefix":"10.1093","volume":"182","author":[{"given":"Chia-Yu","family":"Yang","sequence":"first","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nai-Hui","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Mou","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Immunology Research Center, National Health Research Institutes , Zhunan,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiang-Ju","family":"Min","sequence":"additional","affiliation":[{"name":"Graduate Institute of Cell and Molecular Biology, Taipei Medical University , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey Jong-Young","family":"Yen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical Center"},{"name":"Institute of Biomedical Sciences, Academia Sinica , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan-Shih","family":"Liao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical Center"},{"name":"Institute of Molecular Biology"},{"name":"Graduate Institute of Cell and Molecular Biology, Taipei Medical University , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Fang","family":"Yang-Yen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical Center"},{"name":"Institute of Molecular Biology"},{"name":"Graduate Institute of Cell and Molecular Biology, Taipei Medical University , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,3,1]]},"reference":[{"key":"2026012807041319800_R1","first-page":"3516","article-title":"MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2.","volume-title":"Proc. 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