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Bcl11a is essential for normal lymphoid development

Nature Immunology volume 4, pages 525–532 (2003)Cite this article

Abstract

Bcl11a (also called Evi9) functions as a myeloid or B cell proto-oncogene in mice and humans, respectively. Here we show that Bcl11a is essential for postnatal development and normal lymphopoiesis. Bcl11a mutant embryos lack B cells and have alterations in several types of T cells. Phenotypic and expression studies show that Bcl11a functions upstream of the transcription factors Ebf1 and Pax5 in the B cell pathway. Transplantation studies show that these defects in Bcl11a mutant mice are intrinsic to fetal liver precursor cells. Mice transplanted with Bcl11a-deficient cells died from T cell leukemia derived from the host. Thus, Bcl11a may also function as a non-autonomous T cell tumor suppressor gene.

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Figure 1: Generation and characterization of Bcl11a mutant mice.
Figure 2: Lymphocyte development in Bcl11a mutant embryos.
Figure 3: Impaired B and T cell development in mice transplanted with Bcl11a mutant fetal liver cells.
Figure 4: T cell leukemia in mice transplanted with Bcl11a mutant fetal liver cells.
Figure 5: Histopathological analyses of leukemia in mice receiving transplants.
Figure 6: Enhanced Notch1 expression in the leukemia cells.

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Acknowledgements

We thank S. Spence and T. Kuwata for reviewing the manuscript; D. Swing for help with mouse breeding; J. Wine for tail vein injection; K. Noer and R. Matthai for help with flow cytometry; and the Publication Department of NCI Frederick for graphic illustration. This work was supported by the NCI, Department of Health and Human Services (P.L., N.A.J., N.G.C.). This publication has been funded in whole or in part with federal funds from the NCI, NIH, under contract number NO1-CO-12400 (J.R.K., M.O.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products or organizations imply endorsement by the US Government.

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Authors and Affiliations

  1. Mouse Cancer Genetics Program, National Cancer Institute-Frederick, Maryland, 21702, USA

    Pentao Liu, Lino Tessarollo, Rivka A Rachel, Nancy A Jenkins & Neal G Copeland

  2. Basic Research Program, SAIC-Frederick, Inc, NCI-Frederick, Maryland, 21702, USA

    Jonathan R Keller & Mariaestela Ortiz

  3. Japanese Foundation for Cancer Research, Toshima-ku, Tokyo, 170-8455, Japan

    Takuro Nakamura

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  1. Pentao Liu
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Correspondence to Neal G Copeland.

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Liu, P., Keller, J., Ortiz, M. et al. Bcl11a is essential for normal lymphoid development. Nat Immunol 4, 525–532 (2003). https://doi.org/10.1038/ni925

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