Inducible gene targeting in mice

A method of gene targeting that allows the inducible inactivation of a target gene in mice is presented. The method uses an interferon-responsive promoter to control the expression of Cre recombinase. Here, Cre was used to delete a segment of the DNA polymerase beta gene flanked by IoxP recombinase recognition sites. Deletion was complete in liver and nearly complete in lymphocytes within a few days, whereas partial deletion was obtained in other tissues. This method can be used for the inducible inactivation of any other gene in vivo.

[1]  A. Copp,et al.  Death before birth: clues from gene knockouts and mutations. , 1995, Trends in genetics : TIG.

[2]  D. Melton,et al.  Gene targeting in the mouse. , 1994, BioEssays : news and reviews in molecular, cellular and developmental biology.

[3]  K. Rajewsky,et al.  Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. , 1994, Science.

[4]  K. Rajewsky,et al.  Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting , 1993, Cell.

[5]  R. Ransohoff,et al.  Interferon-induced antiviral actions and their regulation. , 1993, Advances in virus research.

[6]  B. Koller,et al.  Altering genes in animals by gene targeting. , 1992, Annual review of immunology.

[7]  C. Snapper,et al.  Regulation by interferon alpha of immunoglobulin isotype selection and lymphokine production in mice , 1991, The Journal of experimental medicine.

[8]  B. Williams,et al.  Transcriptional regulation of interferon-stimulated genes. , 1991, European journal of biochemistry.

[9]  R. Perlmutter,et al.  Dissection of thymocyte signaling pathways by in vivo expression of pertussis toxin ADP‐ribosyltransferase. , 1990, The EMBO journal.

[10]  M. Noteborn,et al.  Transgenic mice with intracellular immunity to influenza virus , 1990, Cell.

[11]  M. Aebi,et al.  Organization of the murine Mx gene and characterization of its interferon- and virus-inducible promoter , 1988, Molecular and cellular biology.

[12]  N. Henderson,et al.  Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[13]  D. Valenzuela,et al.  Single amino acid changes that render human IFN‐alpha 2 biologically active on mouse cells. , 1987, The EMBO journal.

[14]  J. Sutcliffe,et al.  Transcriptional activation of the mouse Mx gene by type I interferon , 1986, Molecular and cellular biology.

[15]  N. Sternberg,et al.  Bacteriophage P1 site-specific recombination. I. Recombination between loxP sites. , 1981, Journal of molecular biology.

[16]  I. Gresser On the varied biologic effects of interferon. , 1977, Cellular immunology.

[17]  T. Dougherty Effect of Hormones on Lymphatic Tissue , 1952 .