Chromosomal translocation engineering to recapitulate primary events of human cancer
| Autor: | Rosalind Codrington, Terence H. Rabbitts, Richard Pannell, N. Chan, T. Tanaka, Alan Forster, Soledad Romero Rodríguez, Florencia Cano, C.-H. Nam, Angelika Daser, N. Lobato, Markus Metzler, Lesley F Drynan |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Chromosome engineering
Chromosomal translocation Biology Biochemistry Translocation Genetic Fusion gene Mice Neoplasms Genetics medicine Animals Chromosomes Human Humans Molecular Biology Gene Chromosomal inversion Recombination Genetic Models Genetic Intron Cancer medicine.disease Mice Mutant Strains Disease Models Animal Chromosome Inversion Genetic Engineering Homologous recombination |
| DOI: | 10.1101/sqb.2005.70.008 |
| Popis: | Mouse models of human cancers are important for understanding determinants of overt disease and for "preclinical" development of rational therapeutic strategies; for instance, based on macrodrugs. Chromosomal translocations underlie many human leukemias, sarcomas, and epithelial tumors. We have developed three technologies based on homologous recombination in mouse ES cells to mimic human chromosome translocations. The first, called the knockin method, allows creation of fusion genes like those typical of translocations of human leukemias and sarcomas. Two new conditional chromosomal translocation mimics have been developed. The first is a method for generating reciprocal chromosomal translocations de novo using Cre-loxP recombination (translocator mice). In some cases, there is incompatible gene orientation and the translocator model cannot be applied. We have developed a different model (invertor mice) for these situations. This method consists of introducing an inverted cDNA cassette into the intron of a target gene and bringing the cassette into the correct transcriptional orientation by Cre-loxP recombination. We describe experiments using the translocator model to generate MLL-mediated neoplasias and the invertor method to generate EWS-ERG-mediated cancer. These methods mimic the situation found in human chromosome translocations and provide the framework for design and study of human chromosomal translocations in mice. |
| Databáze: | OpenAIRE |
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