A platform for rapid exploration of aging and diseases in a naturally short-lived vertebrate

Itamar Harel, Bérénice A. Benayoun, Ben Machado, Param Priya Singh, Chi Kuo Hu, Matthew F. Pech, Dario Riccardo Valenzano, Elisa Zhang, Sabrina C. Sharp, Steven E. Artandi, Anne Brunet*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

162 Scopus citations

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.

Original languageAmerican English
Pages (from-to)1013-1026
Number of pages14
JournalCell
Volume160
Issue number5
DOIs
StatePublished - 26 Feb 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc.

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