HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 47, 47104-47109, November 21, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/47/47104    most recent M307496200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by DeYoung, R. A. Articles by Winoto, A. Search for Related Content PubMed PubMed Citation Articles by DeYoung, R. A. Articles by Winoto, A. Social Bookmarking                      What's this?

The Orphan Steroid Receptor Nur77 Family Member Nor-1 Is Essential for Early Mouse Embryogenesis^*

R. Andrea DeYoung, Julie C. Baker¶, Dragana Cado, and Astar Winoto||

From the Department of Molecular and Cell Biology, Division of Immunology, University of California at Berkeley, Berkeley, California 94720-3200 and the ^¶Department of Genetics, Stanford University, Palo Alto, California 94305

Nur77 and its family members, Nor-1 and Nurr1, are orphan steroid receptors implicated in a wide variety of biological processes, including apoptosis and dopamine neuron agenesis. Expression of these family members can be detected at low levels in many tissues but they are expressed at very high levels when cells are stimulated by outside signals, including serum, nerve growth factor, and receptor engagement. Introduction of a dominant negative Nur77 protein that blocks the activities of all family members led to inhibition of apoptosis in T cells. Nur77-deficient mice, however, exhibit no phenotype, and a line of Nor-1 mutant mice was reported to exhibit a mild ear development phenotype but no other gross abnormalities. Here, we report the generation of Nor-1-deficient mice with a block in early embryonic development. Nor-1 is expressed early during embryogenesis, and its loss leads to embryonic lethality around embryonic day 8.5 of gestation. The mutant embryos fail to complete gastrulation and display distinct morphological abnormalities, including a decrease in overall size, developmental delay and an accumulation of mesoderm in the primitive streak during gastrulation. Abnormal expression of a number of early developmental markers and defects in growth or distribution of emerging mesoderm cells were also detected. These data suggest that Nor-1 plays a crucial role in gastrulation.

Received for publication, July 12, 2003 , and in revised form, August 27, 2003.

^* This work was supported in part by the National Institutes of Health Grant RO1 CA66236 (to A. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Current address: Embryology Unit, Children's Medical Research Institute, Locked Bag 23, Wentworthville, NSW 2145, Australia.

^|| To whom correspondence should be addressed. Tel.: 510-642-0217; Fax: 510-642-0468; E-mail: winoto{at}uclink4.berkeley.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Dong, C. L. Yauk, A. Williams, A. Lee, G. R. Douglas, and M. G. Wade Hepatic Gene Expression Changes in Hypothyroid Juvenile Mice: Characterization of a Novel Negative Thyroid-Responsive Element Endocrinology, August 1, 2007; 148(8): 3932 - 3940. [Abstract] [Full Text] [PDF]

				S. D. Cho, K. Yoon, S. Chintharlapalli, M. Abdelrahim, P. Lei, S. Hamilton, S. Khan, S. K. Ramaiah, and S. Safe Nur77 Agonists Induce Proapoptotic Genes and Responses in Colon Cancer Cells through Nuclear Receptor-Dependent and Nuclear Receptor-Independent Pathways Cancer Res., January 15, 2007; 67(2): 674 - 683. [Abstract] [Full Text] [PDF]

				G. Benoit, A. Cooney, V. Giguere, H. Ingraham, M. Lazar, G. Muscat, T. Perlmann, J.-P. Renaud, J. Schwabe, F. Sladek, et al. International Union of Pharmacology. LXVI. Orphan Nuclear Receptors Pharmacol. Rev., December 1, 2006; 58(4): 798 - 836. [Abstract] [Full Text] [PDF]

				T. Kanzleiter, T. Schneider, I. Walter, F. Bolze, C. Eickhorst, G. Heldmaier, S. Klaus, and M. Klingenspor Evidence for Nr4a1 as a cold-induced effector of brown fat thermogenesis Physiol Genomics, December 14, 2005; 24(1): 37 - 44. [Abstract] [Full Text] [PDF]

				Genetically Modified Animals in Endocrinology Endocr. Rev., December 1, 2005; 26(7): 985 - 993. [Abstract] [Full Text] [PDF]

				J. Martinez-Gonzalez and L. Badimon The NR4A subfamily of nuclear receptors: new early genes regulated by growth factors in vascular cells Cardiovasc Res, February 15, 2005; 65(3): 609 - 618. [Abstract] [Full Text] [PDF]

				N. Ke, G. Claassen, D.-H. Yu, A. Albers, W. Fan, P. Tan, M. Grifman, X. Hu, K. DeFife, V. Nguy, et al. Nuclear Hormone Receptor NR4A2 Is Involved in Cell Transformation and Apoptosis Cancer Res., November 15, 2004; 64(22): 8208 - 8212. [Abstract] [Full Text] [PDF]