論文

国際誌
2016年6月13日

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

Scientific reports
  • 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

6
開始ページ
27857
終了ページ
27857
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/srep27857

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.

リンク情報
DOI
https://doi.org/10.1038/srep27857
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27291420
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904192
ID情報
  • DOI : 10.1038/srep27857
  • PubMed ID : 27291420
  • PubMed Central 記事ID : PMC4904192

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