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Molecular and Cellular Biology, July 2001, p. 4598-4603, Vol. 21, No. 14
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.14.4598-4603.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Requirement of CDC45 for Postimplantation Mouse Development

Kenichi Yoshida, Frank Kuo, Elizabeth L. George, Arlene H. Sharpe, and Anindya Dutta^*

Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Received 13 February 2001/Returned for modification 6 April 2001/Accepted 25 April 2001

CDC45 is required for the initiation of DNA replication in Saccharomyces cerevisiae and functions as a DNA polymerase  loading factor in Xenopus, but its role in mammalian DNA replication is unknown. To investigate the genetic and physiological functions of CDC45, we used a gene targeting strategy to generate mice lacking a functional CDC45 gene. Homozygous mutant mice lacking a functional CDC45 gene underwent uterine implantation and induced uterine decidualization but did not develop substantially thereafter. Detailed analysis of CDC45 null embryos cultured in vitro revealed impaired proliferation of the inner cell mass. These findings make CDC45 the only putative replication factor experimentally proven to be essential for mammalian development. The CDC45 gene localizes to human chromosome 22q11.2 in the DiGeorge syndrome critical region (DGCR). Almost 90% of individuals with congenital cardiac and craniofacial defects have a monoallelic deletion in the DGCR that includes CDC45. We report here that heterozygous mutant mice develop into adulthood without any apparent abnormalities, so that it is unlikely that hemizygosity of CDC45 alone is responsible for the cardiac and craniofacial defects in the congenital syndromes.

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^* Corresponding author. Mailing address: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St., Boston, MA 02115. Phone: (617) 278-0468. Fax: (617) 732-7449. E-mail: adutta{at}rics.bwh.harvard.edu.

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Molecular and Cellular Biology, July 2001, p. 4598-4603, Vol. 21, No. 14
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.14.4598-4603.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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