| Literature DB >> 25684364 |
Itamar Harel1, Bérénice A Benayoun1, Ben Machado1, Param Priya Singh1, Chi-Kuo Hu1, Matthew F Pech2, Dario Riccardo Valenzano1, Elisa Zhang1, Sabrina C Sharp1, Steven E Artandi3, Anne Brunet4.
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.Entities:
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Year: 2015 PMID： 25684364 PMCID： PMC4344913 DOI： 10.1016/j.cell.2015.01.038
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582