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Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1

Nature volume 382, pages 635–638 (1996)Cite this article

Abstract

THE chemokines are a large family of small, structurally related cytokines1,2. The physiological importance of most members of this family has yet to be elucidated, although some are inducible inflammatory mediators that determine leukocyte chemotaxis1–5. Pre-B-cell growth-stimulating factor/stromal cell-derived factor-1 (PBSF/SDF-1) is a member of the CXC group of chemokines6,7. PBSF/SDF-1 stimulates proliferation of B-cell progenitors in vitro6 and is constitutively expressed in bone-marrow-derived stromal cells6,7. Here we investigate the physiological roles of PBSF/SDF-1 by generating mutant mice with a targeted disruption of the gene encoding PBSF/SDF-1. We found that mice lacking PBSF/SDF-1 died perinatally and that although the numbers of B-cell progenitors in mutant embryos were severely reduced in fetal liver and bone marrow, myeloid progenitors were reduced only in the bone marrow but not in the fetal liver, indicating that PBSF/SDF-1 is responsible for B-cell lymphopoiesis and bone-marrow myelopoiesis. In addition, the mutants had a cardiac ventricular septal defect. Hence, we have shown that the chemokine PBSF/SDF-1 has several essential functions in development.

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Authors and Affiliations

  1. Department of Immunology, Research Institute, Osaka Medical Centerfor Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, 590-02, Japan

    Takashi Nagasawa, Kazunobu Tachibana & Nobuaki Yoshida

  2. Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamada-oka, Suita, Osaka, 565, Japan

    Takashi Nagasawa & Hitoshi Kikutani

  3. Department of Pathology, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka, 565, Japan

    Seiichi Hirota & Yukihiko Kitamura

  4. Department of Molecular Genetics, Faculty of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto, 606, Japan

    Nobuyuki Takakura & Shin-ichi Nishikawa

  5. Department of Medicine III, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka, 565, Japan

    Tadamitsu Kishimoto

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  1. Takashi Nagasawa
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Nagasawa, T., Hirota, S., Tachibana, K. et al. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1. Nature 382, 635–638 (1996). https://doi.org/10.1038/382635a0

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