Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential.

Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential. Research Abstract Details 

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Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential. Abstract Text:

Amy S Rawls,Alyssa D Gregory,Jill R Woloszynek,Fulu Liu,Daniel C Link,

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.

Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential. Publishing Authors By Initials

AS Rawls,AD Gregory,JR Woloszynek,F Liu,DC Link,

For similar natural sciences: time: time factors research abstracts see: natural sciences: time: time factors research

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Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Blood

VOLUME: 110

Page Numbers: 2414-22

Journal Abbreviation: Blood

ISSN: 0006-4971

DAY: 17

MONTH: 07

YEAR: 2007

Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential. Information

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LANGUAGE: eng

NlmUniqueID: 7603509

Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential. Keywords Mesh Terms:

KEYWORDS: Time Factors

MESH TERMS: metabolism

Chemical & Substance for Abstract: Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential. Information

Substance Name: Sbds protein, mouse

Registry Number: 0

Grant and Affiliation Information for Lentiviral-mediated RNAi inhibition of Sbds in murine hematopoietic progenitors impairs their hematopoietic potential.

AFFILIATION: Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: T32 HL07088-23

ACRONYM: HL

MEDLINETA: Blood

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