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CRISPR/Cas9 engineering of a KIM-1 reporter human proximal tubule cell line

We used the CRISPR/Cas9 system to knock-in reporter transgenes at the kidney injury molecule-1 (KIM-1) locus and isolated human proximal tubule cell (HK-2) clones. PCR verified targeted knock-in of the luciferase and eGFP reporter at the KIM-1 locus. HK-2-KIM-1 reporter cells responded to various st...

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Detalles Bibliográficos
Autores principales: Veach, Ruth Ann, Wilson, Matthew H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160069/
https://www.ncbi.nlm.nih.gov/pubmed/30260998
http://dx.doi.org/10.1371/journal.pone.0204487
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author Veach, Ruth Ann
Wilson, Matthew H.
author_facet Veach, Ruth Ann
Wilson, Matthew H.
author_sort Veach, Ruth Ann
collection PubMed
description We used the CRISPR/Cas9 system to knock-in reporter transgenes at the kidney injury molecule-1 (KIM-1) locus and isolated human proximal tubule cell (HK-2) clones. PCR verified targeted knock-in of the luciferase and eGFP reporter at the KIM-1 locus. HK-2-KIM-1 reporter cells responded to various stimuli including hypoxia, cisplatin, and high glucose, indicative of upregulation of KIM-1 expression. We attempted using CRISPR/Cas9 to also engineer the KIM-1 reporter in telomerase-immortalized human RPTEC cells. However, these cells demonstrated an inability to undergo homologous recombination at the target locus. KIM-1-reporter human proximal tubular cells could be valuable tools in drug discovery for molecules inhibiting kidney injury. Additionally, our gene targeting strategy could be used in other cell lines to evaluate the biology of KIM-1 in vitro or in vivo.
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spelling pubmed-61600692018-10-19 CRISPR/Cas9 engineering of a KIM-1 reporter human proximal tubule cell line Veach, Ruth Ann Wilson, Matthew H. PLoS One Research Article We used the CRISPR/Cas9 system to knock-in reporter transgenes at the kidney injury molecule-1 (KIM-1) locus and isolated human proximal tubule cell (HK-2) clones. PCR verified targeted knock-in of the luciferase and eGFP reporter at the KIM-1 locus. HK-2-KIM-1 reporter cells responded to various stimuli including hypoxia, cisplatin, and high glucose, indicative of upregulation of KIM-1 expression. We attempted using CRISPR/Cas9 to also engineer the KIM-1 reporter in telomerase-immortalized human RPTEC cells. However, these cells demonstrated an inability to undergo homologous recombination at the target locus. KIM-1-reporter human proximal tubular cells could be valuable tools in drug discovery for molecules inhibiting kidney injury. Additionally, our gene targeting strategy could be used in other cell lines to evaluate the biology of KIM-1 in vitro or in vivo. Public Library of Science 2018-09-27 /pmc/articles/PMC6160069/ /pubmed/30260998 http://dx.doi.org/10.1371/journal.pone.0204487 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Veach, Ruth Ann
Wilson, Matthew H.
CRISPR/Cas9 engineering of a KIM-1 reporter human proximal tubule cell line
title CRISPR/Cas9 engineering of a KIM-1 reporter human proximal tubule cell line
title_full CRISPR/Cas9 engineering of a KIM-1 reporter human proximal tubule cell line
title_fullStr CRISPR/Cas9 engineering of a KIM-1 reporter human proximal tubule cell line
title_full_unstemmed CRISPR/Cas9 engineering of a KIM-1 reporter human proximal tubule cell line
title_short CRISPR/Cas9 engineering of a KIM-1 reporter human proximal tubule cell line
title_sort crispr/cas9 engineering of a kim-1 reporter human proximal tubule cell line
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160069/
https://www.ncbi.nlm.nih.gov/pubmed/30260998
http://dx.doi.org/10.1371/journal.pone.0204487
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