TY - JOUR
T1 - A platform for rapid exploration of aging and diseases in a naturally short-lived vertebrate
AU - Harel, Itamar
AU - Benayoun, Bérénice A.
AU - Machado, Ben
AU - Singh, Param Priya
AU - Hu, Chi Kuo
AU - Pech, Matthew F.
AU - Valenzano, Dario Riccardo
AU - Zhang, Elisa
AU - Sharp, Sabrina C.
AU - Artandi, Steven E.
AU - Brunet, Anne
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/2/26
Y1 - 2015/2/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84923362368&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2015.01.038
DO - 10.1016/j.cell.2015.01.038
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C2 - 25684364
AN - SCOPUS:84923362368
SN - 0092-8674
VL - 160
SP - 1013
EP - 1026
JO - Cell
JF - Cell
IS - 5
ER -