title: A mouse model of uterine leiomyosarcoma.
abstract: We are using an approach that is based on the cre/loxP recombination process and involves a binary system of Cre-producing and Cre-responding transgenic mice to achieve ubiquitous or tissue-specific expression of oncoproteins. To develop mouse models of tumorigenesis, Cre-producers are mated with responder animals carrying a dormant oncogene targeted into the 3' untranslated region of the locus encoding cytoplasmic beta-actin (actin cassette). Production of oncoprotein from a bicistronic message is accomplished in bitransgenic progeny by Cre-mediated excision of a segment flanked by loxP sites that is located upstream from the oncogenic sequence. Widespread Cre-dependent activation and expression of an actin-cassette transgene encoding the T antigens of the SV40 early region (SVER) commencing in embryos was compatible with normal development and did not impair viability. However, at approximately 3 months of age, all female animals developed massive uterine leiomyosarcomas, whereas practically all males exhibited enormously enlarged seminal vesicles because of pronounced hyperplasia of the smooth muscle layers. In addition, because of smooth muscle hyperproliferation, marked dilation of the gallbladder was observed in mice of both sexes. To begin exploring aberrant signaling events in the SVER-triggered tumorigenic pathways, we analyzed the expression profile of leiomyosarcomas by DNA microarray analysis.
authors.affiliation: Department of Genetics and Development, Columbia University, New York, New York, USA.
authors.forename: Katerina
authors.initials: K
authors.lastname: Politi
authors.forename: Matthias
authors.initials: M
authors.lastname: Szabolcs
authors.forename: Peter
authors.initials: P
authors.lastname: Fisher
authors.forename: Ana
authors.initials: A
authors.lastname: Kljuic
authors.forename: Thomas
authors.initials: T
authors.lastname: Ludwig
authors.forename: Argiris
authors.initials: A
authors.lastname: Efstratiadis
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005704:Gallbladder / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006965:Hyperplasia / Q000473:pathology; D015151:Immunoblotting; D019426:Integrases / Q000235:genetics; D007889:Leiomyoma / Q000235:genetics / Q000473:pathology; D007890:Leiomyosarcoma / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000473:pathology; D016254:Mutagenesis, Insertional / Q000379:methods*; D020411:Oligonucleotide Array Sequence Analysis; D012669:Seminal Vesicles / Q000473:pathology; D019076:Transgenes; D014594:Uterine Neoplasms / Q000235:genetics / Q000473:pathology*; D014764:Viral Proteins / Q000235:genetics
chemical_list: D000199:Actins; D000952:Antigens, Polyomavirus Transforming; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases