title: Telomere regulation during ageing and tumorigenesis of the grey mouse lemur.
abstract: Telomere erosion leading to replicative senescence has been well documented in human and anthropoid primates, and provides a clue against tumorigenesis. In contrast, other mammals, such as laboratory mice, with short lifespan and low body weight mass have different telomere biology without replicative senescence. We analyzed telomere biology in the grey mouse lemur, a small prosimian model with a relative long lifespan currently used in ageing research. We report an average telomere length by telomere restriction fragment (TRF) among the longest reported so far for a primate species (25-30 kb), but without detectable overall telomere shortening with ageing on blood samples. However, we demonstrate using universal STELA (Single Telomere Length Amplification) the existence of short telomeres, the increase of which, while correlating with ageing might be related to another mechanism than replicative senescence. We also found a low stringency of telomerase restriction in tissues and an ease to immortalize fibroblasts in vitro upon spontaneous telomerase activation. Finally, we describe the first grey mouse lemur cancer cell line showing a dramatic telomere shortening and high telomerase activity associated with polyploidy. Our overall results suggest that telomere biology in grey mouse lemur is an exception among primates, with at best a physiologically limited replicative telomere ageing and closest to that observed in small rodents.
authors.affiliation: Structure et Instabilité des Génomes, Sorbonne Universités, Muséum National d'Histoire Naturelle, Inserm U 1154, CNRS UMR 7196, CP26, 57 rue Cuvier, 75005 Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Trochet
authors.affiliation: Structure et Instabilité des Génomes, Sorbonne Universités, Muséum National d'Histoire Naturelle, Inserm U 1154, CNRS UMR 7196, CP26, 57 rue Cuvier, 75005 Paris, France.
authors.forename: Xénia
authors.initials: X
authors.lastname: Mergui
authors.affiliation: Structure et Instabilité des Génomes, Sorbonne Universités, Muséum National d'Histoire Naturelle, Inserm U 1154, CNRS UMR 7196, CP26, 57 rue Cuvier, 75005 Paris, France.
authors.forename: Ivana
authors.initials: I
authors.lastname: Ivkovic
authors.affiliation: Telomeres and Cancer Laboratory, CNRS UMR 3244, Institut Curie, 26 rue d'Ulm, 75248 Paris, France; UPMC Univ. Paris 06, 75005 Paris, France.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Porreca
authors.affiliation: Institut de Systématique, Evolution, Biodiversité, Sorbonne Universités, Muséum National d'Histoire Naturelle, UMR 7205 CNRS, UPMC Univ. Paris 06, EPHE, 57 rue Cuvier, 75005 Paris, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Gerbault-Seureau
authors.affiliation: Structure et Instabilité des Génomes, Sorbonne Universités, Muséum National d'Histoire Naturelle, Inserm U 1154, CNRS UMR 7196, CP26, 57 rue Cuvier, 75005 Paris, France.
authors.forename: Assitan
authors.initials: A
authors.lastname: Sidibe
authors.affiliation: Institut de Systématique, Evolution, Biodiversité, Sorbonne Universités, Muséum National d'Histoire Naturelle, UMR 7205 CNRS, UPMC Univ. Paris 06, EPHE, 57 rue Cuvier, 75005 Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Richard
authors.affiliation: Telomeres and Cancer Laboratory, CNRS UMR 3244, Institut Curie, 26 rue d'Ulm, 75248 Paris, France; UPMC Univ. Paris 06, 75005 Paris, France.
authors.forename: Arturo
authors.initials: A
authors.lastname: Londono-Vallejo
authors.affiliation: Mécanismes Adaptatifs et Evolution, Muséum National d'Histoire Naturelle, Sorbonne Universités, UMR 7179 CNRS, 1 Avenue du Petit Château, 91800 Brunoy, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Perret
authors.affiliation: Mécanismes Adaptatifs et Evolution, Muséum National d'Histoire Naturelle, Sorbonne Universités, UMR 7179 CNRS, 1 Avenue du Petit Château, 91800 Brunoy, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Aujard
authors.affiliation: Structure et Instabilité des Génomes, Sorbonne Universités, Muséum National d'Histoire Naturelle, Inserm U 1154, CNRS UMR 7196, CP26, 57 rue Cuvier, 75005 Paris, France. Electronic address: riou@mnhn.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Riou
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016922:Cellular Senescence; D016565:Cheirogaleidae; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059505:Telomere Homeostasis
chemical_list: D009363:Neoplasm Proteins; D019098:Telomerase
keywords: Ageing; Grey mouse lemur; Primates; Senescence; Single telomere length amplification; Telomere