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Defects in cardiac outflow tract formation and pro-B-lymphocyte expansion in mice lacking Sox-4

Nature volume 380, pages 711–714 (1996)Cite this article

Abstract

A striking example of the relationship between regulation of transcription and phenotype is the central role of the Y-chromo-somal gene Sry in mammalian sex determination1,2. Sry is the founding member of a large family of so-called Sox genes1,3. During murine embryogenesis, the transcriptional activator Sox-4 is expressed at several sites, but in adult mice expression is restricted to immature B and T lymphocytes4. Using targeted genedisruption, we have found that Sox-4−/− embryos succumb to circulatory failure at day E14. This was a result of impaired development of the endocardial ridges (a specific site of Sox-4 expression) into the semilunar valves and the outlet portion of the muscular ventricular septum. The observed range of septation defects is known as 'common arterial trunk' in man. We studied haemopoiesis in lethally irradiated mice reconstituted with Sox-4−/− fetal liver cells and found that a specific block occurred in B-cell development at the pro-B cell stage. In line with this, the frequency and proliferative capacity of IL-7-responsive B cell progenitors in fetal liver were severely decreased in vitro.

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Author notes

  1. Marco W. Schilham

    Present address: Department of Pediatrics, University Hospital, PO Box 9600, 2300 RC, Leiden, The Netherlands

Authors and Affiliations

  1. Department of Immunology, University Hospital, PO Box 85500, 3508 GA, Utrecht, The Netherlands

    Petra Moerer, Marc van de Wetering & Hans Clevers

  2. Transgenic Mouse Facility, University Hospital, PO Box 85500, 3508 GA, Utrecht, The Netherlands

    Sjef Verbeek

  3. Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Mariëtte A. Oosterwegel & Ada M. Kruisbeek

  4. Department of Anatomy and Embryology, Academic Medical Center,University of Amsterdam, Meibergdreef 15, 1105A2, Amsterdam, The Netherlands

    Jing Ya, Piet A. J. de Boer & Wouter H. Lamers

  5. Unité de Biologie Moléculaire du Gène, Institut Pasteur, 28 rue du Dr Roux, 75024, Paris, Cedex 15, France

    Ana Cumano

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  1. Marco W. Schilham
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Schilham, M., Oosterwegel, M., Moerer, P. et al. Defects in cardiac outflow tract formation and pro-B-lymphocyte expansion in mice lacking Sox-4. Nature 380, 711–714 (1996). https://doi.org/10.1038/380711a0

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