Hint2-flox Mouse
一般名
Hint2-flox
製品ID
S-CKO-14346
背景情報
C57BL/6JCya
系統ID
CKOCMP-68917-Hint2-B6J-VA
状況
このマウス系統を論文で使用する場合は、「Hint2-flox Mouse（カタログ番号S-CKO-14346）はサイアジェンから購入しました。」と引用してください。
製品タイプ
年齢
遺伝子型
性別
数量
標準的な配送方法では、少なくとも3匹のヘテロ接合体キャリアを保証しています。ホモ接合体キャリアや指定された性別の個体の繁殖サービスも利用可能です。
基本情報
系統名
Hint2-flox
系統ID
CKOCMP-68917-Hint2-B6J-VA
遺伝子名
製品ID
S-CKO-14346
遺伝子別名
1190005L05Rik
遺伝子別名
C57BL/6JCya
NCBI ID
修正
Conditional knockout
染色体
Chr 4
表現型
アプリケーション
--
さらに
系統詳細
EnsemblトランスクリプトID
ENSMUST00000030192
NCBIトランスクリプトID
NM_026871
ターゲット領域
Exon 2~5
有効領域の大きさ
~1.3 kb
遺伝子研究の概要
Hint2, or Histidine triad nucleotide-binding protein 2, is a dimeric protein belonging to the histidine triad protein superfamily. Predominantly expressed in the liver, pancreas, and adrenal gland, it localizes to the mitochondrion. Hint2 binds nucleotides and catalyzes the hydrolysis of nucleotidyl substrates. It is a key regulator of multiple biological processes, including mitochondria-dependent apoptosis, mitochondrial protein acetylation, and steroidogenesis [6].
In cardiovascular diseases, Hint2 has shown protective effects. In mouse models, Hint2 overexpression inhibited the MCU complex-mitochondrial calcium overload-mitochondrial fission and apoptosis pathway, attenuating cardiac microvascular ischemia-reperfusion injury [1]. Hint2 overexpressing mice also exhibited reduced myocyte hypertrophy and cardiac dysfunction in response to stress, while Hint2 deficiency in mice worsened the hypertrophic phenotype, suggesting Hint2 alleviates pressure overload-induced cardiac remodelling by influencing mitochondrial complex I [2]. In a myocardial infarction mouse model, Hint2 deficiency led to deteriorative oxidative stress and exacerbated myocardial dysfunction [3].
In diabetes-related research, Hint2 reduced ROS-induced oxidative stress and ferroptosis by regulating MCU in a mouse model of diabetic nephropathy [7].
In cancer, in pancreatic cancer tissues, Hint2 expression was low and related to prognosis. Up-regulation of Hint2 triggered apoptosis, and it could sensitize pancreatic cancer cells to gemcitabine-induced apoptosis [8]. In hepatocellular carcinoma, Hint2 was down-regulated, and low Hint2 expression predicted earlier tumor recurrence [4]. In colorectal carcinoma, Hint2 down-regulation promoted migration and metastasis [5].
In conclusion, Hint2 plays essential roles in multiple biological processes, especially those related to mitochondrial function. Studies using gene knockout or overexpression mouse models have revealed its significance in cardiovascular diseases, diabetes-related kidney diseases, and various cancers. These findings provide potential therapeutic targets for treating these diseases.
References：
1. Li, Su, Chen, Jinxiang, Liu, Muyin, Qian, Juying, Ge, Junbo. 2021. Protective effect of HINT2 on mitochondrial function via repressing MCU complex activation attenuates cardiac microvascular ischemia-reperfusion injury. In Basic research in cardiology, 116, 65. doi:10.1007/s00395-021-00905-4. https://pubmed.ncbi.nlm.nih.gov/34914018/
2. Zhang, Nan, Zhou, Zi-Ying, Meng, Yan-Yan, Chen, Si, Tang, Qi-Zhu. . HINT2 protects against pressure overload-induced cardiac remodelling through mitochondrial pathways. In Journal of cellular and molecular medicine, 28, e18276. doi:10.1111/jcmm.18276. https://pubmed.ncbi.nlm.nih.gov/38546629/
3. Li, Fang, Li, Jingzhe, Hao, Jie, Li, Shanshan, Wang, Bin. 2023. HINT2 deficiency deteriorates oxidative stress in a mouse model of myocardial infarction. In ESC heart failure, 10, 1305-1313. doi:10.1002/ehf2.14292. https://pubmed.ncbi.nlm.nih.gov/36722640/
4. Zhou, Dong-Kai, Qian, Xiao-Hui, Cheng, Jun, Chen, Ling-Hui, Wang, Wei-Lin. . Clinical significance of down-regulated HINT2 in hepatocellular carcinoma. In Medicine, 98, e17815. doi:10.1097/MD.0000000000017815. https://pubmed.ncbi.nlm.nih.gov/31770197/
5. Li, Weihua, Cai, Shaoxin, Wang, Le, Zhou, Biaohuan, Wang, Huan. . HINT2 downregulation promotes colorectal carcinoma migration and metastasis. In Oncotarget, 8, 13521-13531. doi:10.18632/oncotarget.14587. https://pubmed.ncbi.nlm.nih.gov/28088787/
6. Yao, Jiaqi, Miao, Yifan, Zhu, Lv, Lu, Yun, Tang, Wenfu. 2023. Histidine triad nucleotide-binding protein 2: From basic science to clinical implications. In Biochemical pharmacology, 212, 115527. doi:10.1016/j.bcp.2023.115527. https://pubmed.ncbi.nlm.nih.gov/37004779/
7. Bai, Mei, Lu, Wei, Tan, Jun, Mei, Xin. 2024. HINT2 may be One Clinical Significance Target for Patient with Diabetes Mellitus and Reduced ROS-Induced Oxidative Stress and Ferroptosis by MCU. In Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 56, 670-678. doi:10.1055/a-2238-2689. https://pubmed.ncbi.nlm.nih.gov/38286402/
8. Chen, Linghui, Sun, Qiang, Zhou, Dongkai, Zheng, Shusen, Wang, Weilin. 2017. HINT2 triggers mitochondrial Ca2+ influx by regulating the mitochondrial Ca2+ uniporter (MCU) complex and enhances gemcitabine apoptotic effect in pancreatic cancer. In Cancer letters, 411, 106-116. doi:10.1016/j.canlet.2017.09.020. https://pubmed.ncbi.nlm.nih.gov/28947137/
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