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Molecular and Cellular Biology, July 2004, p. 5844-5849, Vol. 24, No. 13
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.13.5844-5849.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The ETS Transcription Factor GABP{alpha} Is Essential for Early Embryogenesis

Sika Ristevski,1* Debra A. O'Leary,1 Anders P. Thornell,2,{dagger} Michael J. Owen,2,{ddagger} Ismail Kola,1,§ and Paul J. Hertzog1

Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Clayton, Victoria 3168, Australia,1 Imperial Cancer Research Fund Laboratories, London WQ2A 3PX, United Kingdom2

Received 23 December 2003/ Returned for modification 24 January 2004/ Accepted 9 April 2004

The ETS transcription factor complex GABP consists of the GABP{alpha} protein, containing an ETS DNA binding domain, and an unrelated GABPß protein, containing a transactivation domain and nuclear localization signal. GABP has been shown in vitro to regulate the expression of nuclear genes involved in mitochondrial respiration and neuromuscular signaling. We investigated the in vivo function of GABP by generating a null mutation in the murine Gabp{alpha} gene. Embryos homozygous for the null Gabp{alpha} allele die prior to implantation, consistent with the broad expression of Gabp{alpha} throughout embryogenesis and in embryonic stem cells. Gabp{alpha}+/– mice demonstrated no detectable phenotype and unaltered protein levels in the panel of tissues examined. This indicates that Gabp{alpha} protein levels are tightly regulated to protect cells from the effects of loss of Gabp complex function. These results show that Gabp{alpha} function is essential and is not compensated for by other ETS transcription factors in the mouse, and they are consistent with a specific requirement for Gabp expression for the maintenance of target genes involved in essential mitochondrial cellular functions during early cleavage events of the embryo.

* Corresponding author. Mailing address: Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash Medical Centre, 246 Clayton Rd., Clayton, Victoria 3168, Australia. Phone: 61 3 9594 7217. Fax: 61 3 9594 7211. E-mail: Sika.Ristevski{at}med.monash.edu.au.

{dagger} Present address: Department of Biochemistry and Biophysics, Stockholm University, S-106 91 Stockholm, Sweden.

{ddagger} Present address: GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire SG1 2NY, United Kingdom.

§ Present address: Pharmacia Corporation, Skokie, IL 60077.

Molecular and Cellular Biology, July 2004, p. 5844-5849, Vol. 24, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.13.5844-5849.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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