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Blood, 12 February 2009, Vol. 113, No. 7, pp. 1444-1454. Prepublished online as a Blood First Edition Paper on October 24, 2008; DOI 10.1182/blood-2008-02-142638. This Article Full Text Full Text (PDF) Supplemental Methods and Figures Additional Supplemental Figures All Versions of this Article: blood-2008-02-142638v1 113/7/1444    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Madan, V. Articles by Fehling, H. J. Search for Related Content PubMed PubMed Citation Articles by Madan, V. Articles by Fehling, H. J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Impaired function of primitive hematopoietic cells in mice lacking the Mixed-Lineage-Leukemia homolog Mll5 Vikas Madan1, Babita Madan1, Urszula Brykczynska2, Frédéric Zilbermann2, Kevin Hogeveen3, Konstanze Döhner4, Hartmut Döhner4, Odile Weber1, Carmen Blum1, Hans-Reimer Rodewald1, Paolo Sassone-Corsi3, Antoine H. F. M. Peters2, and Hans Jörg Fehling1 1 Institute of Immunology, University Clinics Ulm, Ulm, Germany; 2 Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland; 3 Institut de Génétique et de Biologie Moléculaire et Cellulaire, Strasbourg-Illkirch, France; and 4 Department of Internal Medicine III, University Clinics Ulm, Ulm, Germany The human Mixed-Lineage-Leukemia-5 (MLL5) gene is located in a genomic region frequently deleted in patients with myeloid malignancies and encodes a widely expressed nuclear protein most closely related to MLL1, a Trithorax transcriptional regulator with established involvement in leukemogenesis. Although the physiologic function of MLL5 is completely unknown, domain structure and homology to transcriptional regulators with histone methyltransferase activity suggest a role in epigenetic gene regulation. To investigate physiologic functions of Mll5, we have generated a knockout mouse mutant using Cre/loxP technology. Adult homozygous Mll5-deficient mice are obtained at reduced frequency because of postnatal lethality. Surviving animals display a variety of abnormalities, including male infertility, retarded growth, and defects in multiple hematopoietic lineages. Interestingly, Mll5–/– mice die of sublethal whole-body irradiation but can be rescued with wild-type bone marrow grafts. Flow cytometric ana-lysis, bone marrow reconstitution, and in vivo BrdU-labeling experiments reveal numerical, functional, and cell-cycle defects in the lineage-negative Sca-1+, Kit+ (LSK) population, which contains short- and long-term hematopoietic stem cells. Together, these in vivo findings establish several nonredundant functions for Mll5, including an essential role in regulating proliferation and functional integrity of hematopoietic stem/progenitor cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: MLL5 governs hematopoiesis: a step closer Han Liu, Todd D. Westergard, and James J.-D. Hsieh Blood 2009 113: 1395-1396. [Full Text] [PDF] This article has been cited by other articles: S. Sebastian, P. Sreenivas, R. Sambasivan, S. Cheedipudi, P. Kandalla, G. K. Pavlath, and J. Dhawan MLL5, a trithorax homolog, indirectly regulates H3K4 methylation, represses cyclin A2 expression, and promotes myogenic differentiation PNAS, March 24, 2009; 106(12): 4719 - 4724. [Abstract] [Full Text] [PDF] H. Liu, T. D. Westergard, and J. J.-D. Hsieh MLL5 governs hematopoiesis: a step closer Blood, February 12, 2009; 113(7): 1395 - 1396. [Full Text] [PDF]

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