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Molecular and Cellular Biology, February 2004, p. 1022-1032, Vol. 24, No. 3
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.3.1022-1032.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Embryonic Lethality, Decreased Erythropoiesis, and Defective Octamer-Dependent Promoter Activation in Oct-1-Deficient Mice

Victoria E. H. Wang,1 Tara Schmidt,1 Jianzhu Chen,1 Phillip A. Sharp,1,2* and Dean Tantin1

Center for Cancer Research, Massachusetts Institute of Technology,1 McGovern Institute, Cambridge, Massachusetts 02139-43072

Received 6 August 2003/ Returned for modification 27 October 2003/ Accepted 31 October 2003

Oct-1 is a sequence-specific DNA binding transcription factor that is believed to regulate a large group of tissue-specific and ubiquitous genes. Both Oct-1 and the related but tissue-restricted Oct-2 protein bind to a DNA sequence termed the octamer motif (5'-ATGCAAAT-3') with equal affinity in vitro. To address the role of Oct-1 in vivo, an Oct-1-deficient mouse strain was generated by gene targeting. Oct-1-deficient embryos died during gestation, frequently appeared anemic, and suffered from a lack of Ter-119-positive erythroid precursor cells. This defect was cell intrinsic. Fibroblasts derived from these embryos displayed a dramatic decrease in Oct-1 DNA binding activity and a lack of octamer-dependent promoter activity in transient transfection assays. Interestingly, several endogenous genes thought to be regulated by Oct-1 showed no change in expression. When crossed to Oct-2+/- animals, transheterozygotes were recovered at a very low frequency. These findings suggest a critical role for Oct-1 during development and a stringent gene dosage effect with Oct-2 in mediating postnatal survival.

* Corresponding author. Mailing address: Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139-4307. Phone: (617) 253-6421. Fax: (617) 253-3867. E-mail: sharppa{at}mit.edu.

Molecular and Cellular Biology, February 2004, p. 1022-1032, Vol. 24, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.3.1022-1032.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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