Chromosome segregation errors: a double-edged sword - TI Pharma

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Abstract
Chromosomal instability (CIN), the loss and gain of whole chromosomes during cell division, is one
of the hallmarks of solid tumors and has been described to influence tumor formation. Both tissue
context and the level of CIN are thought to determine whether CIN has a tumor promoting or tumor
suppressive function. Moreover, excessive CIN has been described to specifically kill tumor cells in
vitro. Here, we describe the generation of a mouse model in which we will be able to test the effects
on tumor growth of various levels of CIN in different tissues. We have generated two Cre-inducible-
Mps1-Knock-in (CiMKi) mouse models that inducibly express mutant forms of the mitotic checkpoint
kinase Mps1; kinase dead Mps1 (D637A) or an Mps1 point mutant with reduced kinase activity
(T649A). These models will gives us the opportunity to test the effect of different levels of CIN in both
tumorigenesis and tumor growth inhibition in a tissue-specific and temporal manner.
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