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JunB can substitute for Jun in mouse development and cell proliferation

Nature Genetics volume 30, pages 158–166 (2002)Cite this article

Abstract

The Jun and JunB components of the AP-1 transcription factor are known to have antagonistic functions. Here we show, by a knock-in strategy and a transgenic complementation approach, that Junb can substitute for absence of Jun during mouse development. Junb can rescue both liver and cardiac defects in Jun-null mice in a manner dependent on gene dosage. JunB restores the expression of genes regulated by Jun/Fos, but not those regulated by Jun/ATF, thereby rescuing Jun-dependent defects in vivo as well as in primary fibroblasts and fetal hepatoblasts in vitro. Thus, the transcriptionally less active JunB has the potential to substitute for Jun, indicating that the spatial and temporal regulation of expression of the transcription factor AP-1 may be more important than the coding sequence of its components.

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Figure 1: Generation of Junb knock-in mice.
Figure 2: Histological analysis of Junki/ki (ki/ki) and Jun−/−Junb-Tg (−/−Tg) mice.
Figure 3: JunB rescues the proliferation defects of Jun−/− primary fibroblasts.
Figure 4: JunB restores AP-1–mediated transcriptional regulation in Jun−/− primary fibroblasts.
Figure 5: JunB restores normal concentrations of p53 and affects cyclin D1 regulation at the post-transcriptional level in Jun−/− primary fibroblasts.
Figure 6: JunB rescues the proliferation and apoptosis defects of Jun−/− fetal liver hepatoblasts.

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Acknowledgements

We are grateful to H.C. Theuβl for ES cell injections; to M. Yaniv (Pasteur Institute, Paris) for the JunB monoclonal antibody; to M. Oren for the p53 promoter construct; to R. Müller for the cyclin D1 promoter construct; to H. vanDam for the 5xJun2–luc reporter; and to M.-H. Idarraga-Amado and D. Mayr for maintaining our mouse colonies. We thank M. Bouchard, H. van Dam, M. Karin, M. Schreiber and M. Sibilia for critically reading the manuscript, and members of the Wagner laboratory for stimulating discussions and assistance. The Institute of Molecular Pathology is supported by Boehringer-Ingelheim, and this work was partly funded by the Austrian Research Foundation, by a TMR network grant from the European Economic Community and by a Marie Curie Fellowship from the European Community to W.J.

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Author notes

  1. Emmanuelle Passegué

    Present address: Department of Pathology, Stanford University, B265 Beckman Center, Stanford, California, 94305, USA

  2. Wolfram Jochum

    Present address: Institute of Clinical Pathology, University Hospital, Schmelzbergstrasse 12, CH-8091, Zürich, Switzerland

  3. Axel Behrens

    Present address: ICRF, Mammalian Genetics Laboratory, 44, Lincoln's Inn Fields, London, WC2A 3PX, UK

Authors and Affiliations

  1. Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, Vienna, A-1030, Austria

    Emmanuelle Passegué, Wolfram Jochum, Axel Behrens, Romeo Ricci & Erwin F. Wagner

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Correspondence to Erwin F. Wagner.

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Passegué, E., Jochum, W., Behrens, A. et al. JunB can substitute for Jun in mouse development and cell proliferation. Nat Genet 30, 158–166 (2002). https://doi.org/10.1038/ng790

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