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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #153508
Title: THE EMBRYONIC FUNCTION OF GERM CELL NUCLEAR FACTOR IS DEPENDENT ON THE DNA BINDING DOMAIN

Author
item LAN, ZI-JIAN - BAYLOR COLL OF MEDICINE
item CHUNG, ARTHUR C-K - BAYLOR COLL OF MEDICINE
item XU, XUEPING - BAYLOR COLL OF MEDICINE
item DEMAYO, FRANCESCO - BAYLOR COLL OF MEDICINE
item COONEY, AUSTIN - BAYLOR COLL OF MEDICINE

Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/18/2002
Publication Date: 12/27/2002
Citation: LAN, Z., CHUNG, A., XU, X., DEMAYO, F.J., COONEY, A.J. THE EMBRYONIC FUNCTION OF GERM CELL NUCLEAR FACTOR IS DEPENDENT ON THE DNA BINDING DOMAIN. JOURNAL OF BIOLOGICAL CHEMISTRY. 2002. v. 277. p. 50660-50667.

Interpretive Summary: GCNF is a steroid receptor like factor. This paper by Lan and others is a peer reviewed article that describes the inactivation of a gene called GCNF in the mouse. In this particular study we have taken away a small part of the GCNF gene. This is enough to inactivate the normal function of the gene. Loss of this factor leads to loss of mouse fetuses during pregnancy. Analysis of these mouse fetuses showed there was multiple problems.

Technical Abstract: Germ cell nuclear factor (GCNF), an orphan nuclear receptor, is essential for mouse embryogenesis. GCNF specifically binds to a DR0 response element via its DNA binding domain (DBD) in vitro and functions as a repressor of gene transcription. To further study the role of GCNF during embryogenesis, we have employed a Cre/loxP strategy and generated a line of GCNF mutant mice (GCNF(lox/lox)) in which the 243-base pair DBD-encoding exon has been deleted in the germline. However, the ligand binding domain (LBD) of GCNF is still expressed at the mRNA and protein levels in the GCNF(lox/lox) mice. GCNF(lox/lox) mice die at 9.5-10.5 days postcoitum. The tailbuds of these mutant embryos protrude outside the yolk sac. Expression of Oct-4 in the somatic cells of GCNF(lox/lox) embryos at 8.25 days postcoitum was not silenced as in the GCNF(+/+) embryos. Therefore, GCNF(lox/lox) mice phenocopy the GCNF(-/-) mice. Our results indicate that the DBD is essential for the function of GCNF during early mouse embryogenesis, and that the LBD does not mediate any function independent of the DBD at this stage of embryonic development. Our results also suggest that GCNF is indeed a transcriptional factor that represses gene transcription mediated via its DBD.