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Hyperlipidemia and hepatitis in liver-specific CREB3L3 knockout mice generated using a one-step CRISPR/Cas9 system
Description
<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>Creb3l3</jats:italic> 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 <jats:italic>Srebf2</jats:italic> 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.</jats:p>
Journal
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- Scientific Reports
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Scientific Reports 6 27857-, 2016-06
Nature Publishing Group
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Keywords
- Male
- Hyperlipidemias
- Hepatitis, Animal
- Article
- Mice
- Methionine
- Non-alcoholic Fatty Liver Disease
- Intestine, Small
- Animals
- Insulin
- Cyclic AMP Response Element-Binding Protein
- Triglycerides
- Mice, Knockout
- Choline Deficiency
- Up-Regulation
- Mice, Inbred C57BL
- Cholesterol
- Liver
- Female
- CRISPR-Cas Systems
- Sterol Regulatory Element Binding Protein 2
Details 詳細情報について
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- CRID
- 1050282677631331712
-
- ISSN
- 20452322
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- HANDLE
- 2241/00143325
-
- PubMed
- 27291420
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- Text Lang
- en
-
- Article Type
- journal article
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- Data Source
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- IRDB
- Crossref
- KAKEN
- OpenAIRE