Hes5-KO 基因敲除小鼠

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产品名称

Hes5-KO 基因敲除小鼠

产品编号

S-KO-02438

品系全称

C57BL/6JCya-Hes5em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-15208-Hes5-B6J-VA

品系状态

使用本品系发表的文献需注明: Hes5-KO 基因敲除小鼠 mice (Strain S-KO-02438) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
KO小鼠库模型
Notch信号通路

基本信息

基因研究概述

质控标准

基因
基因全称
hes family bHLH transcription factor 5
基因别称
bHLHb38
染色体号
Chr 4 (Mouse)
转录本 ID
NCBI: NM_010419 | Ensembl: ENSMUST00000049621
修饰方式
全身性基因敲除
靶向范围
Exon 1~3
敲除长度
~1.5 kb
品系说明
该品系是基于策略设计时的数据库信息制作而成,建议您在购买前查询最新的数据库和相关文献,以获取最准确的表型信息。
表型提示
MGI:104876Mice homozygous for disruptions in this gene are phenotypically normal although there are subtile histological abnormalities associated with sensory organs.
Hes5,也称为Hairy and enhancer of split 5,是一种重要的碱性螺旋-环-螺旋(bHLH)转录抑制因子。Hes5在多种生物学过程中发挥重要作用,包括细胞分化、发育、代谢和疾病发生。Hes5是Notch信号通路的下游效应因子,通过直接与DNA结合,抑制目标基因的表达,从而调控细胞命运和细胞状态的维持。

在肿瘤发生中,Hes5表现出复杂的生物学功能。一方面,Hes5可以通过抑制Notch信号通路下游基因HES1的表达,以及下调与细胞增殖相关的基因如MYC的靶基因ODC1和LDHA的表达,从而抑制肿瘤的发生和发展。另一方面,Hes5也可以通过促进AKT依赖的肝脏肿瘤形成和干细胞特征,从而促进肿瘤的发生和发展。

Hes5在神经系统发育中也发挥重要作用。Hes5可以与细胞特异性转录激活因子Sox10相互作用,通过转录抑制和直接隔离Sox10蛋白,进一步降低Sox10的生物利用度,从而抑制髓鞘基因的表达。同时,随着Sox10表达水平的增加,Sox10可以与Hes5结合,通过隔离和从髓鞘启动子中置换抑制性复合物,抵消Hes5的抑制作用。

此外,Hes5还在其他生物学过程中发挥重要作用。例如,在缺氧诱导的肺动脉高压中,Notch3/Hes5信号通路可以通过激活氧化和内质网应激以及下游的氧化还原信号通路,导致血管功能障碍和肺动脉高压的发生。在人类脑类器官中,Hes5是GLI3的直接靶基因,参与调节脑区域的形成和神经发生。

综上所述,Hes5是一种重要的转录抑制因子,参与调控多种生物学过程,包括细胞分化、发育、代谢和疾病发生。Hes5的生物学功能复杂多样,既可以抑制肿瘤的发生和发展,也可以促进肿瘤的发生和发展。Hes5的研究有助于深入理解转录调控的生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略[1][2][3][4][5][6][7][8][9][10]。

参考文献:
1. Luiken, Sarah, Fraas, Angelika, Bieg, Matthias, Longerich, Thomas, Roessler, Stephanie. 2020. NOTCH target gene HES5 mediates oncogenic and tumor suppressive functions in hepatocarcinogenesis. In Oncogene, 39, 3128-3144. doi:10.1038/s41388-020-1198-3. https://pubmed.ncbi.nlm.nih.gov/32055024/
2. Kuretani, Aya, Yamamoto, Takayoshi, Taira, Masanori, Michiue, Tatsuo. 2021. Evolution of hes gene family in vertebrates: the hes5 cluster genes have specifically increased in frogs. In BMC ecology and evolution, 21, 147. doi:10.1186/s12862-021-01879-6. https://pubmed.ncbi.nlm.nih.gov/34325655/
3. Liu, Aixiao, Li, Jiadong, Marin-Husstege, Mireya, Gelinas, Celine, Casaccia-Bonnefil, Patrizia. 2006. A molecular insight of Hes5-dependent inhibition of myelin gene expression: old partners and new players. In The EMBO journal, 25, 4833-42. doi:. https://pubmed.ncbi.nlm.nih.gov/17006542/
4. Morris, Hannah E, Neves, Karla B, Nilsen, Margaret, MacLean, Margaret R, Touyz, Rhian M. 2023. Notch3/Hes5 Induces Vascular Dysfunction in Hypoxia-Induced Pulmonary Hypertension Through ER Stress and Redox-Sensitive Pathways. In Hypertension (Dallas, Tex. : 1979), 80, 1683-1696. doi:10.1161/HYPERTENSIONAHA.122.20449. https://pubmed.ncbi.nlm.nih.gov/37254738/
5. Fleck, Jonas Simon, Jansen, Sophie Martina Johanna, Wollny, Damian, Camp, J Gray, Treutlein, Barbara. 2022. Inferring and perturbing cell fate regulomes in human brain organoids. In Nature, 621, 365-372. doi:10.1038/s41586-022-05279-8. https://pubmed.ncbi.nlm.nih.gov/36198796/
6. Liu, Jia, Lu, Wei-Guo, Ye, Feng, Chen, Huai-zeng, Xie, Xing. . Hes1/Hes5 gene inhibits differentiation via down-regulating Hash1 and promotes proliferation in cervical carcinoma cells. In International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 20, 1109-16. doi:. https://pubmed.ncbi.nlm.nih.gov/21495212/
7. Su, Yi-Xun, Hou, Cong-Cong, Yang, Wan-Xi. 2014. Control of hair cell development by molecular pathways involving Atoh1, Hes1 and Hes5. In Gene, 558, 6-24. doi:10.1016/j.gene.2014.12.054. https://pubmed.ncbi.nlm.nih.gov/25550047/
8. Choi, Eun-Bee, Vodnala, Munender, Saini, Prince, Inouye, Carla, Fong, Yick W. 2023. Transcription factor SOX15 regulates stem cell pluripotency and promotes neural fate during differentiation by activating the neurogenic gene Hes5. In The Journal of biological chemistry, 299, 102996. doi:10.1016/j.jbc.2023.102996. https://pubmed.ncbi.nlm.nih.gov/36764520/
9. Wang, Xinyu, Fu, Yajuan, Chen, Xiaoduan, Lü, Weiguo, Xie, Xing. 2009. The expressions of bHLH gene HES1 and HES5 in advanced ovarian serous adenocarcinomas and their prognostic significance: a retrospective clinical study. In Journal of cancer research and clinical oncology, 136, 989-96. doi:10.1007/s00432-009-0744-8. https://pubmed.ncbi.nlm.nih.gov/20091184/
10. Jaszczyk, Aneta, Stankiewicz, Adrian M, Goscik, Joanna, Jezierski, Tadeusz, Juszczak, Grzegorz R. 2023. Overnight Corticosterone and Gene Expression in Mouse Hippocampus: Time Course during Resting Period. In International journal of molecular sciences, 24, . doi:10.3390/ijms24032828. https://pubmed.ncbi.nlm.nih.gov/36769150/