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Mice with reduced expression of the telomere-associated protein Ft1 develop p53-sensitive progeroid traits

Abstract : Human AKTIP and mouse Ft1 are orthologous ubiquitin E2 variant proteins involved in telomere maintenance and DNA replication. AKTIP also interacts with A- and B-type lamins. These features suggest that Ft1 may be implicated in aging regulatory pathways. Here, we show that cells derived from hypomorph Ft1 mutant (Ft1kof/kof ) mice exhibit telomeric defects and that Ft1kof/kof animals develop progeroid traits, including impaired growth, skeletal and skin defects, abnormal heart tissue, and sterility. We also demonstrate a genetic interaction between Ft1 and p53. The analysis of mice carrying mutations in both Ft1 and p53 (Ft1kof/kof ; p53ko/ko and Ft1kof/kof ; p53+/ko ) showed that reduction in p53 rescues the progeroid traits of Ft1 mutants, suggesting that they are at least in part caused by a p53-dependent DNA damage response. Conversely, Ft1 reduction alters lymphomagenesis in p53 mutant mice. These results identify Ft1 as a new player in the aging process and open the way to the analysis of its interactions with other progeria genes using the mouse model.
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Submitted on : Tuesday, April 17, 2018 - 10:34:22 AM
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Mattia La Torre, Chiara Merigliano, Romina Burla, Carla Mottini, Giorgia Zanetti, et al.. Mice with reduced expression of the telomere-associated protein Ft1 develop p53-sensitive progeroid traits. Aging Cell, Wiley Open Access, In press, pp.e12730. ⟨10.1111/acel.12730⟩. ⟨pasteur-01768324⟩

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