國家衛生研究院 NHRI:Item 3990099045/4343
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/4343


    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
    Authors: Yang, CY;Lin, NH;Lee, JM;Huang, CY;Min, HJ;Yen, JJY;Liao, NS;Yang-Yen, HF
    Contributors: Immunology Research Center
    Abstract: We previously demonstrated that IL-3 stimulates transcription of the antiapoptotic gene mcl-1 via two promoter elements designated its 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. The Journal of Immunology, 2009, 182: 2959-2968.
    Date: 2009-03
    Relation: Journal of Immunology. 2009 Mar;182(5):2959-2968.
    Link to: http://dx.doi.org/10.4049/jimmunol.0803550
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-1767&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000263653100046
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=64849107994
    Appears in Collections:[Ching-Yu Huang] Periodical Articles

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