A Mouse Model of Uterine Leiomyosarcoma

作者: Katerina Politi , Matthias Szabolcs , Peter Fisher , Ana Kljuic , Thomas Ludwig

DOI: 10.1016/S0002-9440(10)63122-7

关键词: Untranslated regionGene expression profilingPathologyCre recombinaseCarcinogenesisCell biologyGenetically modified mouseBiologyActinTransgeneOncogene

摘要: We are using an approach that is based on the cre/loxP recombination process and involves a binary system of Cre-producing Cre-responding transgenic mice to achieve ubiquitous or tissue-specific expression oncoproteins. To develop mouse models tumorigenesis, Cre-producers mated with responder animals carrying dormant oncogene targeted into 3′ untranslated region locus encoding cytoplasmic β-actin (actin cassette). Production oncoprotein from bicistronic message accomplished in bitransgenic progeny by Cre-mediated excision segment flanked loxP sites located upstream oncogenic sequence. Widespread Cre-dependent activation actin-cassette transgene T antigens SV40 early (SVER) commencing embryos was compatible normal development did not impair viability. However, at ∼3 months age, all female developed massive uterine leiomyosarcomas, whereas practically males exhibited enormously enlarged seminal vesicles because pronounced hyperplasia smooth muscle layers. In addition, hyperproliferation, marked dilation gallbladder observed both sexes. begin exploring aberrant signaling events SVER-triggered tumorigenic pathways, we analyzed profile leiomyosarcomas DNA microarray analysis.

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