A transgenic mouse strain expressing four drug-selectable marker genes.

Murine embryonic stem (ES) cells are commonly cultured on feeder layers of primary murine embryonic fibroblasts (MEFs). Because gene targeting experiments often involve sequential selection for multiple-drug resistance in single ES cell lines, we have developed a new mouse strain which represents an economical donor for the production of multiple-drug resistant MEFs. MEFs prepared from the DR-4 mouse strain displayed resistance to concentrations of the drugs G418, 6-thioguanine, puromycin and hygromycin well above those used normally for the selection of drug-resistant ES cells.

[1]  Muriel T. Davisson,et al.  Genetic variation among 129 substrains and its importance for targeted mutagenesis in mice , 1997, Nature Genetics.

[2]  R. Jaenisch,et al.  Complementation of methylation deficiency in embryonic stem cells by a DNA methyltransferase minigene. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[3]  R. Jaenisch,et al.  De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. , 1996, Development.

[4]  R. Jaenisch,et al.  Germ-line passage is required for establishment of methylation and expression patterns of imprinted but not of nonimprinted genes. , 1996, Genes & development.

[5]  F. Sablitzky,et al.  Inducible site-directed recombination in mouse embryonic stem cells. , 1996, Nucleic acids research.

[6]  E. Simpson,et al.  Transgenic mice for the preparation of hygromycin-resistant primary embryonic fibroblast feeder layers for embryonic stem cell selections. , 1995, Nucleic acids research.

[7]  Rudolf Jaenisch,et al.  Targeted mutation of the DNA methyltransferase gene results in embryonic lethality , 1992, Cell.

[8]  M. Rudnicki,et al.  The mouse Pgk-1 gene promoter contains an upstream activator sequence. , 1991, Nucleic acids research.

[9]  A. Berns,et al.  Consecutive inactivation of both alleles of the pim-1 proto-oncogene by homologous recombination in embryonic stem cells , 1990, Nature.

[10]  R. Jaenisch,et al.  Germ-line transmission of a disrupted β2microglobulin gene produced by homologous recombination in embryonic stem cells , 1989, Nature.

[11]  A. Clarke,et al.  Germ line transmission and expression of a corrected HPRT gene produced by gene targeting in embryonic stem cells , 1989, Cell.

[12]  M. Capecchi,et al.  Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells , 1987, Cell.

[13]  M. Monk,et al.  HPRT-deficient (Lesch–Nyhan) mouse embryos derived from germline colonization by cultured cells , 1987, Nature.

[14]  E. Robertson.  Teratocarcinomas and embryonic stem cells : a practical approach , 1987 .