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Molecular and Cellular Biology, October 2001, p. 6549-6558, Vol. 21, No. 19
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.19.6549-6558.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The Ornithine Decarboxylase Gene Is Essential for Cell Survival during Early Murine Development

Hélène Pendeville,1,2 Nick Carpino,1 Jean-Christophe Marine,1,3 Yutaka Takahashi,1 Marc Muller,2 Joseph A. Martial,2 and John L. Cleveland1,4,*

Department of Biochemistry1 and Howard Hughes Medical Institute,3 St. Jude Children's Research Hospital, Memphis, Tennessee 38105; Department of Molecular Sciences, University of Tennessee, Memphis, Tennessee 381634; and Laboratoire de Biologie Moléculaire et de Génie Génétique, Institut de Chimie, Université de Liège, B-4000 Sart-Tilman, Belgium2

Received 29 March 2001/Returned for modification 6 June 2001/Accepted 2 July 2001

Overexpression and inhibitor studies have suggested that the c-Myc target gene for ornithine decarboxylase (ODC), the enzyme which converts ornithine to putrescine, plays an important role in diverse biological processes, including cell growth, differentiation, transformation, and apoptosis. To explore the physiological function of ODC in mammalian development, we generated mice harboring a disrupted ODC gene. ODC-heterozygous mice were viable, normal, and fertile. Although zygotic ODC is expressed throughout the embryo prior to implantation, loss of ODC did not block normal development to the blastocyst stage. Embryonic day E3.5 ODC-deficient embryos were capable of uterine implantation and induced maternal decidualization yet failed to develop substantially thereafter. Surprisingly, analysis of ODC-deficient blastocysts suggests that loss of ODC does not affect cell growth per se but rather is required for survival of the pluripotent cells of the inner cell mass. Therefore, ODC plays an essential role in murine development, and proper homeostasis of polyamine pools appears to be required for cell survival prior to gastrulation.

* Corresponding author. Mailing address: Department of Biochemistry, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105. Phone: (901) 495-2398. Fax: (901) 525-8025. E-mail: john.cleveland{at}stjude.org.

Molecular and Cellular Biology, October 2001, p. 6549-6558, Vol. 21, No. 19
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.19.6549-6558.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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