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A platform for rapid exploration of aging and diseases in a naturally short-lived vertebrate.
Harel, Itamar; Benayoun, Bérénice A; Machado, Ben; Singh, Param Priya; Hu, Chi-Kuo; Pech, Matthew F; Valenzano, Dario Riccardo; Zhang, Elisa; Sharp, Sabrina C; Artandi, Steven E; Brunet, Anne.
Afiliación
  • Harel I; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Benayoun BA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Machado B; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Singh PP; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Hu CK; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Pech MF; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Biochemistry Department, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Valenzano DR; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Zhang E; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Sharp SC; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • Artandi SE; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Biochemistry Department, Stanford University School of Medicine, Stanford, CA 94305, USA; Glenn Laboratories for the Biology of Aging at Stanford, Stanford, CA 94305, USA.
  • Brunet A; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Glenn Laboratories for the Biology of Aging at Stanford, Stanford, CA 94305, USA. Electronic address: abrunet1@stanford.edu.
Cell ; 160(5): 1013-1026, 2015 Feb 26.
Article en En | MEDLINE | ID: mdl-25684364
ABSTRACT
VIDEO ABSTRACT Aging is a complex process that affects multiple organs. Modeling aging and age-related diseases in the lab is challenging because classical vertebrate models have relatively long lifespans. Here, we develop the first platform for rapid exploration of age-dependent traits and diseases in vertebrates, using the naturally short-lived African turquoise killifish. We provide an integrative genomic and genome-editing toolkit in this organism using our de-novo-assembled genome and the CRISPR/Cas9 technology. We mutate many genes encompassing the hallmarks of aging, and for a subset, we produce stable lines within 2-3 months. As a proof of principle, we show that fish deficient for the protein subunit of telomerase exhibit the fastest onset of telomere-related pathologies among vertebrates. We further demonstrate the feasibility of creating specific genetic variants. This genome-to-phenotype platform represents a unique resource for studying vertebrate aging and disease in a high-throughput manner and for investigating candidates arising from human genome-wide studies.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Peces Killi Límite: Animals / Female / Humans / Male Idioma: En Revista: Cell Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Peces Killi Límite: Animals / Female / Humans / Male Idioma: En Revista: Cell Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos