Targeted oncogene activation by site-specific recombination in transgenic mice.
An efficient and accurate method for controlled in vivo transgene modulation by site-directed recombination is described. Seven transgenic mouse founder lines were produced carrying the murine lens-specific alpha A-crystallin promoter and the simian virus 40 large tumor-antigen gene sequence, separated by a 1.3-kilobase-pair Stop sequence that contains elements preventing expression of the large tumor-antigen gene and Cre recombinase recognition sites. Progeny from two of these lines were mated with transgenic mice expressing the Cre recombinase under control of either the murine alpha A-crystallin promoter or the human cytomegalovirus promoter. All double-transgenic offspring developed lens tumors. Subsequent analysis confirmed that tumor formation resulted from large tumor-antigen activation via site-specific, Cre-mediated deletion of Stop sequences.
Lakso
M
M
Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Sauer
B
B
Mosinger
B
B
Lee
E J
EJ
Manning
R W
RW
Yu
S H
SH
Mulder
K L
KL
Westphal
H
H
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D001483:Base Sequence; D002386:Cataract / Q000235:genetics; D004254:DNA Nucleotidyltransferases / Q000235:genetics; D005134:Eye Neoplasms / Q000235:genetics; D019426:Integrases; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009857:Oncogenes; D011995:Recombination, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014764:Viral Proteins
D000952:Antigens, Polyomavirus Transforming; D009838:Oligodeoxyribonucleotides; D014764:Viral Proteins; C045073:Cre recombinase; D004254:DNA Nucleotidyltransferases; D019426:Integrases