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Vol. 13, No. 12, pp. 1524-1528, June 15, 1999

RESEARCH COMMUNICATION
Targeting genes for self-excision in the germ line

Michaeline Bunting,1 Kenneth E. Bernstein,2 Joy M. Greer,3 Mario R. Capecchi,3 and Kirk R. Thomas3,4

1 Hematology Division, Department of Internal Medicine, University of Utah, Salt Lake City, Utah 84112 USA; 2 Department of Pathology, Emory University, Atlanta, Georgia 30322 USA; 3 Howard Hughes Medical Institute, Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah 84112 USA

A procedure is described that directs the self-induced deletion of DNA sequences as they pass through the male germ line of mice. The testes-specific promoter from the angiotensin-converting enzyme gene was used to drive expression of the Cre-recombinase gene. Cre was linked to the selectable marker Neor, and the two genes flanked with loxP elements. This cassette was targeted to the Hoxa3 gene in mouse ES cells that were in turn used to generate chimeric mice. In these chimeras, somatic cells derived from the ES cells retained the cassette, but self-excision occurred in all ES-cell-derived sperm.

[Key Words: Targeted gene modification; conditional mutagenesis; gene therapy; Cre/loxP; angiotensin-converting enzyme]


GENES & DEVELOPMENT 13:1524-1528 © 1999 by Cold Spring Harbor Laboratory Press  ISSN 0890-9369/99 $5.00

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