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Cell. 2015 Feb 26;160(5):1013-26. doi: 10.1016/j.cell.2015.01.038. Epub 2015 Feb 12.

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

Author information

  • 1Department of Genetics, Stanford University, Stanford, CA 94305, USA.
  • 2Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Biochemistry Department, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 3Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA; Biochemistry Department, Stanford University School of Medicine, Stanford, CA 94305, USA; Glenn Laboratories for the Biology of Aging at Stanford, Stanford, CA 94305, USA.
  • 4Department of Genetics, Stanford University, Stanford, CA 94305, USA; Glenn Laboratories for the Biology of Aging at Stanford, Stanford, CA 94305, USA. Electronic address: abrunet1@stanford.edu.

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.

Copyright © 2015 Elsevier Inc. All rights reserved.

PMID:
25684364
[PubMed - indexed for MEDLINE]
PMCID:
PMC4344913
Free PMC Article
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