Aph1a-flox 基因敲除小鼠

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产品名称

Aph1a-flox 基因敲除小鼠

产品编号

S-CKO-06960

品系全称

C57BL/6JCya-Aph1aem1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-226548-Aph1a-B6J-VA

品系状态

使用本品系发表的文献需注明: Aph1a-flox 基因敲除小鼠 mice (Strain S-CKO-06960) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO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
aph1 homolog A, gamma secretase subunit
基因别称
APH-1a
染色体号
Chr 3 (Mouse)
转录本 ID
NCBI: NM_146104 | Ensembl: ENSMUST00000015894
修饰方式
条件性基因敲除
靶向范围
Exon 2~5
敲除长度
~1.4 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:2385110Homozygous null embryos die by E11, are severely growth retarded by E9.5 and display defects in somite patterning, branchial arch and heart chamber development, vascular morphogenesis of the yolk sac and have distended pericardial sacs.
APH1a,也称为anterior pharynx defective 1A,是一种重要的蛋白质,参与γ-分泌酶复合物的形成和功能。γ-分泌酶复合物是一种多蛋白、跨膜切割蛋白酶,负责切割多种蛋白质底物,包括Notch受体和淀粉样前体蛋白。γ-分泌酶复合物由四个主要成分组成:presenilin (PS)、nicastrin (NCT)、pen-2 (Pen2)和APH1。APH1a是APH1家族的一个成员,与APH1b一起,参与γ-分泌酶复合物的组装和功能。

γ-分泌酶复合物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。Notch信号通路是γ-分泌酶复合物的一个主要底物,参与调节细胞命运决定、细胞增殖和细胞凋亡。淀粉样前体蛋白是另一种γ-分泌酶复合物的底物,其切割产生β-淀粉样蛋白,是阿尔茨海默病的主要致病因素。

APH1a在γ-分泌酶复合物的组装和功能中发挥重要作用。APH1a与PS、NCT和Pen2相互作用,参与γ-分泌酶复合物的形成和稳定。APH1a的缺失或突变会导致γ-分泌酶复合物活性降低,从而影响Notch信号通路和淀粉样前体蛋白的加工。

此外,APH1a还与其他蛋白质相互作用,参与其他生物学过程。例如,APH1a可以与microRNA-151-5p相互作用,参与调节海马体中恐惧记忆的形成。miR-151-5p水平的升高可以抑制APH1a的表达,从而影响海马体中恐惧记忆的形成。

在疾病研究中,APH1a也受到关注。研究发现,APH1a的表达与胰腺癌的预后相关,APH1a表达升高与较差的预后相关。此外,APH1a的表达与慢性阻塞性肺病(COPD)和肺功能相关,一个现有的小分子抑制剂可以增加FEV1。

APH1a是一种重要的蛋白质,参与γ-分泌酶复合物的形成和功能。APH1a在多种生物学过程中发挥重要作用,包括Notch信号通路和淀粉样前体蛋白的加工。此外,APH1a还与其他蛋白质相互作用,参与其他生物学过程。在疾病研究中,APH1a也受到关注,其表达与胰腺癌、COPD和肺功能相关。APH1a的研究有助于深入理解γ-分泌酶复合物的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. Wang, Zihui, Li, Shaoqiang, Cai, Guannan, Hu, Jieying, Zheng, Jinping. 2024. Mendelian randomization analysis identifies druggable genes and drugs repurposing for chronic obstructive pulmonary disease. In Frontiers in cellular and infection microbiology, 14, 1386506. doi:10.3389/fcimb.2024.1386506. https://pubmed.ncbi.nlm.nih.gov/38660492/
2. Xu, Xu-Feng, Wang, You-Cui, Zong, Liang, Wang, Xiao-Long. 2019. miR-151-5p modulates APH1a expression to participate in contextual fear memory formation. In RNA biology, 16, 282-294. doi:10.1080/15476286.2019.1572435. https://pubmed.ncbi.nlm.nih.gov/30663934/
3. Yu, Hongyan, Zhang, Haisan, Yang, Yongfeng, Yang, Ge, Lü, Luxian. . [Association of gene polymorphisms with the susceptibility of schizophrenia in Han Chinese population]. In Zhonghua yi xue za zhi, 95, 3803-7. doi:. https://pubmed.ncbi.nlm.nih.gov/27337794/
4. Sun, Xiaohui, Ping, Jie, Guo, Xingyi, Shu, Xiao-Ou, Shu, Xiang. 2024. Drug-target Mendelian randomization revealed a significant association of genetically proxied metformin effects with increased prostate cancer risk. In Molecular carcinogenesis, 63, 849-858. doi:10.1002/mc.23692. https://pubmed.ncbi.nlm.nih.gov/38517045/
5. Jeon, Yun Ho, Ha, Mihyang, Kim, Sung Won, Oh, Sae-Ock, Kim, Yun Hak. 2019. Evaluation of the prognostic significances of γ-secretase genes in pancreatic cancer. In Oncology letters, 17, 4614-4620. doi:10.3892/ol.2019.10113. https://pubmed.ncbi.nlm.nih.gov/30944650/
6. Zhao, Guojun, Liu, Zhenyi, Ilagan, Ma Xenia G, Kopan, Raphael. . Gamma-secretase composed of PS1/Pen2/Aph1a can cleave notch and amyloid precursor protein in the absence of nicastrin. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 30, 1648-56. doi:10.1523/JNEUROSCI.3826-09.2010. https://pubmed.ncbi.nlm.nih.gov/20130175/
7. Dunys, Julie, Kawarai, Toshitaka, Wilk, Sherwin, Alves da Costa, Cristine, Checler, Frédéric. . Catabolism of endogenous and overexpressed APH1a and PEN2: evidence for artifactual involvement of the proteasome in the degradation of overexpressed proteins. In The Biochemical journal, 394, 501-9. doi:. https://pubmed.ncbi.nlm.nih.gov/16302845/
8. Vural, S, Baumgartner, M, Lichtner, P, Wagner, M, Giehl, K A. 2021. Investigation of gamma secretase gene complex mutations in German population with Hidradenitis suppurativa designate a complex polygenic heritage. In Journal of the European Academy of Dermatology and Venereology : JEADV, 35, 1386-1392. doi:10.1111/jdv.17163. https://pubmed.ncbi.nlm.nih.gov/33559291/
9. Osathanon, Thanaphum, Manokawinchoke, Jeeranan, Sa-Ard-Iam, Noppadol, Pavasant, Prasit, Suwanwela, Jaijam. 2019. Jagged1 promotes mineralization in human bone-derived cells. In Archives of oral biology, 99, 134-140. doi:10.1016/j.archoralbio.2019.01.013. https://pubmed.ncbi.nlm.nih.gov/30682716/
10. Guo, Jin-Hu, Cheng, Hai-Peng, Yu, Long, Zhao, Shouyuan. . Natural antisense transcripts of Alzheimer's disease associated genes. In DNA sequence : the journal of DNA sequencing and mapping, 17, 170-3. doi:. https://pubmed.ncbi.nlm.nih.gov/17076261/