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Blood, 1 October 2007, Vol. 110, No. 7, pp. 2414-2422. Prepublished online as a Blood First Edition Paper on July 17, 2007; DOI 10.1182/blood-2006-03-007112. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-03-007112v1 110/7/2414    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 Rawls, A. S. Articles by Link, D. C. Search for Related Content PubMed PubMed Citation Articles by Rawls, A. S. Articles by Link, D. C. Related Collections Hematopoiesis and Stem Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential Amy S. Rawls1, Alyssa D. Gregory1, Jill R. Woloszynek1, Fulu Liu1, and Daniel C. Link1 1 Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO Shwachman-Diamond syndrome (SDS) is a rare multisystem disorder characterized by exocrine pancreatic insufficiency, multilineage hematopoietic dysfunction, and metaphyseal chondrodysplasia. Bone marrow dysfunction is present in nearly all patients with SDS, with neutropenia being the most common abnormality. The majority of patients with SDS have mutations in the Shwachman Bodian Diamond syndrome (SBDS) gene. We have developed a strategy to examine the consequences of lentiviral-mediated RNA interference (RNAi) of Sbds on hematopoiesis. Here, we report that both Sbds RNA and protein expression can be efficiently inhibited in primary murine hematopoietic cells using lentiviral-mediated RNAi. Inhibition of Sbds results in a defect in granulocytic differentiation in vitro and impairs myeloid progenitor generation in vivo. In addition, short-term hematopoietic engraftment was impaired, which is due in part to reduced homing of hematopoietic progenitors to the bone marrow. Finally, we show that inhibition of Sbds is associated with a decrease in circulating B lymphocytes, despite evidence of normal B lymphopoiesis. These data provide the first evidence that loss of Sbds is sufficient to induce abnormalities in hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. T. Calado and N. S. Young Telomere maintenance and human bone marrow failure Blood, May 1, 2008; 111(9): 4446 - 4455. [Abstract] [Full Text] [PDF]

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