title: A platform for rapid exploration of aging and diseases in a naturally short-lived vertebrate.
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.
authors: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors: Itamar
authors: I
authors: Harel
authors: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors: Bérénice A
authors: BA
authors: Benayoun
authors: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors: Ben
authors: B
authors: Machado
authors: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors: Param Priya
authors: PP
authors: Singh
authors: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors: Chi-Kuo
authors: CK
authors: Hu
authors: Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Biochemistry Department, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: Matthew F
authors: MF
authors: Pech
authors: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors: Dario Riccardo
authors: DR
authors: Valenzano
authors: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors: Elisa
authors: E
authors: Zhang
authors: Department of Genetics, Stanford University, Stanford, CA 94305, USA.
authors: Sabrina C
authors: SC
authors: Sharp
authors: 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.
authors: Steven E
authors: SE
authors: Artandi
authors: 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.
authors: Anne
authors: A
authors: Brunet
mesh_terms: D000375:Aging; D000818:Animals; D001483:Base Sequence; D064113:CRISPR-Cas Systems; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D005260:Female; D005821:Genetic Techniques; D006801:Humans; D007695:Killifishes / Q000235:genetics / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D008969:Molecular Sequence Data; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D014714:Vertebrates / Q000502:physiology
chemical_list: D019098:Telomerase; D004259:DNA-Directed DNA Polymerase