Ontology highlight
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.
SUBMITTER: Harel I
PROVIDER: S-EPMC4344913 | biostudies-literature | 2015 Feb
REPOSITORIES: biostudies-literature
Harel Itamar I Benayoun Bérénice A BA Machado Ben B Singh Param Priya PP Hu Chi-Kuo CK Pech Matthew F MF Valenzano Dario Riccardo DR Zhang Elisa E Sharp Sabrina C SC Artandi Steven E SE Brunet Anne A
Cell 20150212 5
<h4>Video abstract</h4>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 a ...[more]