Mutant mice lacking the p53 C-terminal domain model telomere syndromes.

摘要: Mutations in p53, although frequent human cancers, have not been implicated telomere-related syndromes. Here, we show that homozygous mutant mice expressing p53Δ31, a p53 lacking the C-terminal domain, exhibit increased activity and suffer from aplastic anemia pulmonary fibrosis, hallmarks of syndromes caused by short telomeres. Indeed, p53Δ31/Δ31 had telomeres other phenotypic traits associated with telomere disease dyskeratosis congenita its severe variant Hoyeraal-Hreidarsson syndrome. Heterozygous p53+/Δ31 were only mildly affected, but decreased levels Mdm4, negative regulator led to dramatic aggravation their symptoms. Importantly, several genes involved metabolism downregulated cells, including Dyskerin, Rtel1, Tinf2, which are mutated congenita, Terf1, is anemia. Together, these data reveal truncating mutation can activate plays major role regulation metabolism.