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dc.contributor.authorJarrett, Kelsey E.
Lee, Ciaran M.
Yeh, Yi-Hsien
Hsu, Rachel H.
Gupta, Rajat
Zhang, Min
Rodriguez, Perla J.
Lee, Chang Seok
Gillard, Baiba K.
Bissig, Karl-Dimiter
Pownall, Henry J.
Martin, James F.
Bao, Gang
Lagor, William R.
dc.date.accessioned 2017-04-04T17:30:17Z
dc.date.available 2017-04-04T17:30:17Z
dc.date.issued 2017
dc.identifier.citation Jarrett, Kelsey E., Lee, Ciaran M., Yeh, Yi-Hsien, et al.. "Somatic genome editing with CRISPR/Cas9 generates and corrects a metabolic disease." Scientific Reports, 4, (2017) Springer Nature: https://doi.org/10.1038/srep44624.
dc.identifier.urihttps://hdl.handle.net/1911/94050
dc.description.abstract Germline manipulation using CRISPR/Cas9 genome editing has dramatically accelerated the generation of new mouse models. Nonetheless, many metabolic disease models still depend upon laborious germline targeting, and are further complicated by the need to avoid developmental phenotypes. We sought to address these experimental limitations by generating somatic mutations in the adult liver using CRISPR/Cas9, as a new strategy to model metabolic disorders. As proof-of-principle, we targeted the low-density lipoprotein receptor (Ldlr), which when deleted, leads to severe hypercholesterolemia and atherosclerosis. Here we show that hepatic disruption of Ldlr with AAV-CRISPR results in severe hypercholesterolemia and atherosclerosis. We further demonstrate that co-disruption of Apob, whose germline loss is embryonically lethal, completely prevented disease through compensatory inhibition of hepatic LDL production. This new concept of metabolic disease modeling by somatic genome editing could be applied to many other systemic as well as liver-restricted disorders which are difficult to study by germline manipulation.
dc.language.iso eng
dc.publisher Springer Nature
dc.rights This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the articleメs Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.title Somatic genome editing with CRISPR/Cas9 generates and corrects a metabolic disease
dc.type Journal article
dc.citation.journalTitle Scientific Reports
dc.citation.volumeNumber 4
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1038/srep44624
dc.identifier.pmcid PMC5353616
dc.identifier.pmid 28300165
dc.type.publication publisher version
dc.citation.articleNumber 44624


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This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the articleメs Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.
Except where otherwise noted, this item's license is described as This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the articleメs Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.