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Molecular and Cellular Biology, January 2003, p. 38-54, Vol. 23, No. 1
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.1.38-54.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Mammalian SIR2{alpha} Protein Has a Role in Embryogenesis and Gametogenesis

Michael W. McBurney,1* Xiaofeng Yang,1 Karen Jardine,1 Mary Hixon,2 Kim Boekelheide,2 John R. Webb,3 Peter M. Lansdorp,4 and Madeleine Lemieux1

Ottawa Regional Cancer Centre and Department of Medicine, University of OttawaOttawa, Ontario K1H 1C4,1 Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa K1H 8M5,3 Terry Fox Laboratory, British Columbia Cancer Research Center, and Department of Medicine, University of British Columbia, Vancouver, British Columbia V5Z 1L3, Canada,4 Department of Pathology, Brown University, Providence, Rhode Island 029122

Received 3 July 2002/ Returned for modification 4 September 2002/ Accepted 1 October 2002

The yeast Sir2p protein has an essential role in maintaining telomeric and mating type genes in their transcriptionally inactive state. Mammalian cells have a very large proportion of their genome inactive and also contain seven genes that have regions of homology with the yeast sir2 gene. One of these mammalian genes, sir2{alpha}, is the presumptive mammalian homologue of the yeast sir2 gene. We set out to determine if sir2{alpha} plays a role in mammalian gene silencing by creating a strain of mice carrying a null allele of sir2{alpha}. Animals carrying two null alleles of sir2{alpha} were smaller than normal at birth, and most died during the early postnatal period. In an outbred background, the sir2{alpha} null animals often survived to adulthood, but both sexes were sterile. We found no evidence for failure of gene silencing in sir2{alpha} null animals, suggesting that either SIR2{alpha} has a different role in mammals than it does in Saccharomyces cerevisiae or that its role in gene silencing in confined to a small subset of mammalian genes. The phenotype of the sir2{alpha} null animals suggests that the SIR2{alpha} protein is essential for normal embryogenesis and for normal reproduction in both sexes.

* Corresponding author. Mailing address: Ottawa Regional Cancer Centre, 503 Smyth Road, Ottawa, Canada K1H 1C4. Phone: (613) 737-7700, x6887. Fax: (613) 247-3524. E-mail: michael.mcburney{at}orcc.on.ca.

Molecular and Cellular Biology, January 2003, p. 38-54, Vol. 23, No. 1
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.1.38-54.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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