CRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice

Abstract The p53 mutation and altered Pten expression are two most common genetic events in Hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC). To confirm the causative role of p53 and Pten somatic mutation in HCC development, we established CRISPR/Cas9-mediated somatic gene di...

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Autores principales:	Yongzhen Liu, Xuewei Qi, Zhenzhen Zeng, Lu Wang, Jie Wang, Ting Zhang, Qiang Xu, Congle Shen, Guangde Zhou, Shaomin Yang, Xiangmei Chen, Fengmin Lu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c96c68288ad24689b9cc13fabef5e8ba
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spelling	oai:doaj.org-article:c96c68288ad24689b9cc13fabef5e8ba2021-12-02T11:52:34ZCRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice10.1038/s41598-017-03070-82045-2322https://doaj.org/article/c96c68288ad24689b9cc13fabef5e8ba2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03070-8https://doaj.org/toc/2045-2322Abstract The p53 mutation and altered Pten expression are two most common genetic events in Hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC). To confirm the causative role of p53 and Pten somatic mutation in HCC development, we established CRISPR/Cas9-mediated somatic gene disruption via hydrodynamic tail vein injection, allowing for in vivo targeting p53 and Pten simultaneously in adult HBV transgenic mice. Here we demonstrated that the utility of this approach resulted in macroscopic liver tumors as early as 4 months’ post injection and most tumors harbored both p53 and Pten loss-of-function alterations. Immunohistochemical (IHC) and histopathology analysis demonstrated that the tumors were positive for Glutamine synthetase (GS), a marker of HCC and accompanied with prominent lipid accumulation. The study here indicated that CRISPR/Cas9-mediated p53 and Pten somatic mutation accelerated hepatocarcinogenesis in adult HBV transgenic mice. This method also provides a fast and convenient system for generating mouse model of HCC with HBV infection characteristics.Yongzhen LiuXuewei QiZhenzhen ZengLu WangJie WangTing ZhangQiang XuCongle ShenGuangde ZhouShaomin YangXiangmei ChenFengmin LuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yongzhen Liu Xuewei Qi Zhenzhen Zeng Lu Wang Jie Wang Ting Zhang Qiang Xu Congle Shen Guangde Zhou Shaomin Yang Xiangmei Chen Fengmin Lu CRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice
description	Abstract The p53 mutation and altered Pten expression are two most common genetic events in Hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC). To confirm the causative role of p53 and Pten somatic mutation in HCC development, we established CRISPR/Cas9-mediated somatic gene disruption via hydrodynamic tail vein injection, allowing for in vivo targeting p53 and Pten simultaneously in adult HBV transgenic mice. Here we demonstrated that the utility of this approach resulted in macroscopic liver tumors as early as 4 months’ post injection and most tumors harbored both p53 and Pten loss-of-function alterations. Immunohistochemical (IHC) and histopathology analysis demonstrated that the tumors were positive for Glutamine synthetase (GS), a marker of HCC and accompanied with prominent lipid accumulation. The study here indicated that CRISPR/Cas9-mediated p53 and Pten somatic mutation accelerated hepatocarcinogenesis in adult HBV transgenic mice. This method also provides a fast and convenient system for generating mouse model of HCC with HBV infection characteristics.
format	article
author	Yongzhen Liu Xuewei Qi Zhenzhen Zeng Lu Wang Jie Wang Ting Zhang Qiang Xu Congle Shen Guangde Zhou Shaomin Yang Xiangmei Chen Fengmin Lu
author_facet	Yongzhen Liu Xuewei Qi Zhenzhen Zeng Lu Wang Jie Wang Ting Zhang Qiang Xu Congle Shen Guangde Zhou Shaomin Yang Xiangmei Chen Fengmin Lu
author_sort	Yongzhen Liu
title	CRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice
title_short	CRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice
title_full	CRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice
title_fullStr	CRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice
title_full_unstemmed	CRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice
title_sort	crispr/cas9-mediated p53 and pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis b virus transgenic mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c96c68288ad24689b9cc13fabef5e8ba
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CRISPR/Cas9-mediated p53 and Pten dual mutation accelerates hepatocarcinogenesis in adult hepatitis B virus transgenic mice

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