Hyperlipidemia and hepatitis in liver-specific CREB3L3 knockout mice generated using a one-step CRISPR/Cas9 system

Yoshimi Nakagawa; Fusaka Oikawa; Seiya Mizuno; Hiroshi Ohno; Yuka Yagishita; Aoi Satoh; Yoshinori Osaki; Kenta Takei; Takuya Kikuchi; Song Iee Han; Takashi Matsuzaka; Hitoshi Iwasaki; Kazuto Kobayashi; Shigeru Yatoh; Naoya Yahagi; Masaaki Isaka; Hiroaki Suzuki; Hirohito Sone; Satoru Takahashi; Nobuhiro Yamada; Hitoshi Shimano

doi:10.1038/srep27857

Hyperlipidemia and hepatitis in liver-specific CREB3L3 knockout mice generated using a one-step CRISPR/Cas9 system

Yoshimi Nakagawa, Fusaka Oikawa, Seiya Mizuno, Hiroshi Ohno, Yuka Yagishita, Aoi Satoh, Yoshinori Osaki, Kenta Takei, Takuya Kikuchi, Song Iee Han, Takashi Matsuzaka, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Naoya Yahagi, Masaaki Isaka, Hiroaki Suzuki, Hirohito Sone, Satoru Takahashi, Nobuhiro Yamada^*Hitoshi Shimano

^*Corresponding author for this work

Complex Biosystem Research, Institute of Natural Medicine

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

cAMP responsive element binding protein 3-like 3 (CREB3L3), a transcription factor expressed in the liver and small intestine, governs fasting-response energy homeostasis. Tissue-specific CREB3L3 knockout mice have not been generated till date. To our knowledge, this is the first study using the one-step CRISPR/Cas9 system to generate CREB3L3 floxed mice and subsequently obtain liver-and small intestine-specific Creb3l3 knockout (LKO and IKO, respectively) mice. While LKO mice as well as global KO mice developed hypertriglyceridemia, LKO mice exhibited hypercholesterolemia in contrast to hypocholesterolemia in global KO mice. LKO mice demonstrated up-regulation of hepatic Srebf2 and its corresponding target genes. No phenotypic differences were observed between IKO and floxed mice. Severe liver injury was observed in LKO mice fed a methionine-choline deficient diet, a model for non-alcoholic steatohepatitis. These results provide new evidence regarding the hepatic CREB3L3 role in plasma triglyceride metabolism and hepatic and intestinal CREB3L3 contributions to cholesterol metabolism.

Original language	English
Article number	27857
Journal	Scientific Reports
Volume	6
DOIs	https://doi.org/10.1038/srep27857
State	Published - 2016/06/13

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Nakagawa, Y., Oikawa, F., Mizuno, S., Ohno, H., Yagishita, Y., Satoh, A., Osaki, Y., Takei, K., Kikuchi, T., Han, S. I., Matsuzaka, T., Iwasaki, H., Kobayashi, K., Yatoh, S., Yahagi, N., Isaka, M., Suzuki, H., Sone, H., Takahashi, S., ... Shimano, H. (2016). Hyperlipidemia and hepatitis in liver-specific CREB3L3 knockout mice generated using a one-step CRISPR/Cas9 system. Scientific Reports, 6, Article 27857. https://doi.org/10.1038/srep27857

@article{547a72bb3b6e425e8306b495844a2422,

title = "Hyperlipidemia and hepatitis in liver-specific CREB3L3 knockout mice generated using a one-step CRISPR/Cas9 system",

abstract = "cAMP responsive element binding protein 3-like 3 (CREB3L3), a transcription factor expressed in the liver and small intestine, governs fasting-response energy homeostasis. Tissue-specific CREB3L3 knockout mice have not been generated till date. To our knowledge, this is the first study using the one-step CRISPR/Cas9 system to generate CREB3L3 floxed mice and subsequently obtain liver-and small intestine-specific Creb3l3 knockout (LKO and IKO, respectively) mice. While LKO mice as well as global KO mice developed hypertriglyceridemia, LKO mice exhibited hypercholesterolemia in contrast to hypocholesterolemia in global KO mice. LKO mice demonstrated up-regulation of hepatic Srebf2 and its corresponding target genes. No phenotypic differences were observed between IKO and floxed mice. Severe liver injury was observed in LKO mice fed a methionine-choline deficient diet, a model for non-alcoholic steatohepatitis. These results provide new evidence regarding the hepatic CREB3L3 role in plasma triglyceride metabolism and hepatic and intestinal CREB3L3 contributions to cholesterol metabolism.",

author = "Yoshimi Nakagawa and Fusaka Oikawa and Seiya Mizuno and Hiroshi Ohno and Yuka Yagishita and Aoi Satoh and Yoshinori Osaki and Kenta Takei and Takuya Kikuchi and Han, {Song Iee} and Takashi Matsuzaka and Hitoshi Iwasaki and Kazuto Kobayashi and Shigeru Yatoh and Naoya Yahagi and Masaaki Isaka and Hiroaki Suzuki and Hirohito Sone and Satoru Takahashi and Nobuhiro Yamada and Hitoshi Shimano",

year = "2016",

month = jun,

day = "13",

doi = "10.1038/srep27857",

language = "英語",

volume = "6",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Research",

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Nakagawa, Y, Oikawa, F, Mizuno, S, Ohno, H, Yagishita, Y, Satoh, A, Osaki, Y, Takei, K, Kikuchi, T, Han, SI, Matsuzaka, T, Iwasaki, H, Kobayashi, K, Yatoh, S, Yahagi, N, Isaka, M, Suzuki, H, Sone, H, Takahashi, S, Yamada, N & Shimano, H 2016, 'Hyperlipidemia and hepatitis in liver-specific CREB3L3 knockout mice generated using a one-step CRISPR/Cas9 system', Scientific Reports, vol. 6, 27857. https://doi.org/10.1038/srep27857

TY - JOUR

T1 - Hyperlipidemia and hepatitis in liver-specific CREB3L3 knockout mice generated using a one-step CRISPR/Cas9 system

AU - Nakagawa, Yoshimi

AU - Oikawa, Fusaka

AU - Mizuno, Seiya

AU - Ohno, Hiroshi

AU - Yagishita, Yuka

AU - Satoh, Aoi

AU - Osaki, Yoshinori

AU - Takei, Kenta

AU - Kikuchi, Takuya

AU - Han, Song Iee

AU - Matsuzaka, Takashi

AU - Iwasaki, Hitoshi

AU - Kobayashi, Kazuto

AU - Yatoh, Shigeru

AU - Yahagi, Naoya

AU - Isaka, Masaaki

AU - Suzuki, Hiroaki

AU - Sone, Hirohito

AU - Takahashi, Satoru

AU - Yamada, Nobuhiro

AU - Shimano, Hitoshi

PY - 2016/6/13

Y1 - 2016/6/13

N2 - cAMP responsive element binding protein 3-like 3 (CREB3L3), a transcription factor expressed in the liver and small intestine, governs fasting-response energy homeostasis. Tissue-specific CREB3L3 knockout mice have not been generated till date. To our knowledge, this is the first study using the one-step CRISPR/Cas9 system to generate CREB3L3 floxed mice and subsequently obtain liver-and small intestine-specific Creb3l3 knockout (LKO and IKO, respectively) mice. While LKO mice as well as global KO mice developed hypertriglyceridemia, LKO mice exhibited hypercholesterolemia in contrast to hypocholesterolemia in global KO mice. LKO mice demonstrated up-regulation of hepatic Srebf2 and its corresponding target genes. No phenotypic differences were observed between IKO and floxed mice. Severe liver injury was observed in LKO mice fed a methionine-choline deficient diet, a model for non-alcoholic steatohepatitis. These results provide new evidence regarding the hepatic CREB3L3 role in plasma triglyceride metabolism and hepatic and intestinal CREB3L3 contributions to cholesterol metabolism.

AB - cAMP responsive element binding protein 3-like 3 (CREB3L3), a transcription factor expressed in the liver and small intestine, governs fasting-response energy homeostasis. Tissue-specific CREB3L3 knockout mice have not been generated till date. To our knowledge, this is the first study using the one-step CRISPR/Cas9 system to generate CREB3L3 floxed mice and subsequently obtain liver-and small intestine-specific Creb3l3 knockout (LKO and IKO, respectively) mice. While LKO mice as well as global KO mice developed hypertriglyceridemia, LKO mice exhibited hypercholesterolemia in contrast to hypocholesterolemia in global KO mice. LKO mice demonstrated up-regulation of hepatic Srebf2 and its corresponding target genes. No phenotypic differences were observed between IKO and floxed mice. Severe liver injury was observed in LKO mice fed a methionine-choline deficient diet, a model for non-alcoholic steatohepatitis. These results provide new evidence regarding the hepatic CREB3L3 role in plasma triglyceride metabolism and hepatic and intestinal CREB3L3 contributions to cholesterol metabolism.

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U2 - 10.1038/srep27857

DO - 10.1038/srep27857

M3 - 学術論文

C2 - 27291420

AN - SCOPUS:84974725578

SN - 2045-2322

VL - 6

JO - Scientific Reports

JF - Scientific Reports

M1 - 27857

ER -

Hyperlipidemia and hepatitis in liver-specific CREB3L3 knockout mice generated using a one-step CRISPR/Cas9 system

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