C57BL/6JCya-Hint2em1flox/Cya
Common Name:
Hint2-flox
Product ID:
S-CKO-14346
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Hint2-flox
Strain ID
CKOCMP-68917-Hint2-B6J-VA
Gene Name
Product ID
S-CKO-14346
Gene Alias
1190005L05Rik
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
4
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Hint2em1flox/Cya mice (Catalog S-CKO-14346) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000030192
NCBI RefSeq
NM_026871
Target Region
Exon 2~5
Size of Effective Region
~1.3 kb
Detailed Document
Overview of Gene Research
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/
Quality Control Standard
Sperm Test
Pre-cryopreservation: Measurement of sperm concentration, determination of sperm viability.
Post-cryopreservation: A vial of cryopreserved sperms is selected for in-vitro fertilization from each batch.
Environmental Standards:SPF
Available Region:Global
Source:Cyagen