A Platform for Rapid Exploration of Aging and Diseases in a Naturally Short-Lived Vertebrate

被引：169

作者：

Harel, Itamar ^{[1
]}

Benayoun, Berenice A. ^{[1
]}

Machado, Ben ^{[1
]}

Singh, Param Priya ^{[1
]}

Hu, Chi-Kuo ^{[1
]}

Pech, Matthew F. ^{[2
,3
]}

Valenzano, Dario Riccardo ^{[1
]}

Zhang, Elisa ^{[1
]}

Sharp, Sabrina C. ^{[1
]}

Artandi, Steven E. ^{[2
,3
,4
]}

Brunet, Anne ^{[1
,4
]}

机构：

[1] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA

[4] Glenn Labs Biol Aging Stanford, Stanford, CA 94305 USA

来源：

CELL | 2015年 / 160卷 / 05期

关键词：

FISH NOTHOBRANCHIUS-FURZERI; TELOMERASE; GENOME; GENETICS; MODEL; BIOLOGY; LONGEVITY; CANCER; RATS; LIFE;

D O I：

10.1016/j.cell.2015.01.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1013 / 1026

页数：14

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