title: Generation of mice with longer and better preserved telomeres in the absence of genetic manipulations.
abstract: Although telomere length is genetically determined, mouse embryonic stem (ES) cells with telomeres of twice the normal size have been generated. Here, we use such ES cells with 'hyper-long' telomeres, which also express green fluorescent protein (GFP), to generate chimaeric mice containing cells with both hyper-long and normal telomeres. We show that chimaeric mice contain GFP-positive cells in all mouse tissues, display normal tissue histology and normal survival. Both hyper-long and normal telomeres shorten with age, but GFP-positive cells retain longer telomeres as mice age. Chimaeric mice with hyper-long telomeres also accumulate fewer cells with short telomeres and less DNA damage with age, and express lower levels of p53. In highly renewing compartments, such as the blood, cells with hyper-long telomeres are longitudinally maintained or enriched with age. We further show that wound-healing rates in the skin are increased in chimaeric mice. Our work demonstrates that mice with functional, longer and better preserved telomeres can be generated without the need for genetic manipulations, such as TERT overexpression.
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, Madrid E-28029, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Varela
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, Madrid E-28029, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Muñoz-Lorente
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, Madrid E-28029, Spain.
authors.forename: Agueda M
authors.initials: AM
authors.lastname: Tejera
authors.affiliation: Transgenics Mice Unit, Biotechnology Program, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, Madrid E-28029, Spain.
authors.forename: Sagrario
authors.initials: S
authors.lastname: Ortega
authors.affiliation: Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, Madrid E-28029, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Blasco
mesh_terms: D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D004249:DNA Damage; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000254:growth & development; D008136:Longevity / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D061251:Primary Cell Culture; D012867:Skin / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D000072836:Surgical Wound; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism; D059505:Telomere Homeostasis; D059506:Telomere Shortening; D014945:Wound Healing / Q000235:genetics*
chemical_list: D049452:Green Fluorescent Proteins