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Molecular and Cellular Biology, March 2002, p. 1919-1925, Vol. 22, No. 6
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.6.1919-1925.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Activating Transcription Factor 1 and CREB Are Important for Cell Survival during Early Mouse Development

Susanne C. Bleckmann, Julie A. Blendy,,{dagger} Dorothea Rudolph,,{ddagger} A. Paula Monaghan,,§ Wolfgang Schmid, and Günther Schütz*

Department of Molecular Biology of the Cell I, German Cancer Research Centre, D-69120 Heidelberg, Germany

Received 10 August 2001/ Returned for modification 10 October 2001/ Accepted 12 December 2001

Activating transcription factor 1 (ATF1), CREB, and the cyclic AMP (cAMP) response element modulatory protein (CREM), which constitute a subfamily of the basic leucine zipper transcription factors, activate gene expression by binding as homo- or heterodimers to the cAMP response element in regulatory regions of target genes. To investigate the function of ATF1 in vivo, we inactivated the corresponding gene by homologous recombination. In contrast to CREB-deficient mice, which suffer from perinatal lethality, mice lacking ATF1 do not exhibit any discernible phenotypic abnormalities. Since ATF1 and CREB but not CREM are strongly coexpressed during early mouse development, we generated mice deficient for both CREB and ATF1. ATF1-/- CREB-/- embryos die before implantation due to developmental arrest. ATF1+/- CREB-/- embryos display a phenotype of embryonic lethality around embryonic day 9.5 due to massive apoptosis. These results indicate that CREB and ATF1 act in concert to mediate signals essential for maintaining cell viability during early embryonic development.

* Corrresponding author. Mailing address: Department of Molecular Biology of the Cell I, German Cancer Research Centre, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. Phone: 49 6221 42 34 22. Fax: 49 6221 42 34 70. E-mail: g.schuetz{at}dkfz.de.

{dagger} Present address: Dept. of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104-6084.

{ddagger} Present address: Departments of Medical Biophysics and Immunology, The Amgen Institute, Ontario Cancer Institute, University of Toronto, Toronto, Ontario M5G 2C1, Canada.

§ Present address: Dept. of Neurobiology, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15261.

Molecular and Cellular Biology, March 2002, p. 1919-1925, Vol. 22, No. 6
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.6.1919-1925.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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