Acute systemic loss of Mad2 leads to intestinal atrophy in adult mice.

摘要: Chromosomal instability (CIN) is a hallmark of cancer, leading to aneuploid cells. To study the role that CIN plays in tumor evolution, several mouse models have been engineered over last 2 decades. These unequivocally shown systemic high-grade embryonic lethal. We and others previously lethality can be circumvented by provoking tissue-specific fashion. In this study, we provoke adult mice as an alternative circumvent lethality. For this, disrupt spindle assembly checkpoint (SAC) alleviating Mad2 or truncating Mps1, both essential genes for SAC functioning, with without p53 inactivation. find disruption leads rapid villous atrophy, atypia apoptosis epithelia jejunum ileum, substantial weight loss, death within 2-3 weeks after start insult. Despite severe intestinal phenotype, most other tissues are unaffected, except minor abnormalities spleen, presumably due lower proliferation rate these tissues. conclude vivo toxic high cell turnover epithelia.