Genetic background and tumour susceptibility in mouse models

Dear Editor,

Genetically engineered mouse (GEM) models of tumourigenesis have revolutionised our understanding of the molecular mechanisms of cancer. They have been instrumental in the identification and characterisation of oncogenes and tumour suppressors and have provided invaluable tools for recapitulating human cancers. However, a major caveat of using GEM models is the phenotypic variation that arises due to the influence of genetic background.^{1, 2} Even after extensive backcrossing (>10 times), genes physically linked to the deleted gene can be the same as those of the ES cells. As we discuss here, differences in genetic background have been shown to significantly impact tumour susceptibility, which can lead to misinterpretation of results. This strain-dependent phenotypic variation can manifest as completely different phenotypes or differential penetrance.^{1, 2}

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