Ssr1-flox 基因敲除小鼠

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产品名称

Ssr1-flox 基因敲除小鼠

产品编号

S-CKO-00575

品系全称

C57BL/6JCya-Ssr1em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-107513-Ssr1-B6J-VA

品系状态

使用本品系发表的文献需注明: Ssr1-flox 基因敲除小鼠 mice (Strain S-CKO-00575) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO小鼠库模型

基本信息

基因研究概述

质控标准

基因
基因全称
signal sequence receptor, alpha
基因别称
2510001K09Rik,6330400D04,SSR,TRAPA
染色体号
Chr 13 (Mouse)
转录本 ID
NCBI: NM_001360842 | Ensembl: ENSMUST00000225246
修饰方式
条件性基因敲除
靶向范围
Exon 2
敲除长度
~2.3 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:105082Homozygous mutation of this gene results in neonatal lethality, subcutaneous edema, and cardiac defects, including absence of septation of the proximal part of the outflow tract, double outlet right ventricle, persistent truncus arteriosis, and abnormal development of the endocardial cushion.
信号序列受体亚基1(Signal Sequence Receptor Subunit 1, SSR1),也称为TRAPα(Translocon-associated protein complex α),是一种重要的细胞内蛋白,属于TRAP(Translocon-associated protein complex)复合物的组成部分。TRAP复合物主要负责在粗面内质网(Endoplasmic Reticulum, ER)膜上对特定蛋白质进行跨膜转运,对蛋白质的合成和折叠过程至关重要[1]。SSR1在哺乳动物的心脏发育中扮演着关键角色,其突变会导致心脏流出道的形态发生缺陷,进而引发严重的先天性心脏病[1]。

除了在心脏发育中的作用外,SSR1在植物中也具有重要作用。研究发现,SSR1在植物的根发育和生长素极性运输中发挥功能。在拟南芥(Arabidopsis thaliana)中,SSR1的突变会导致主根生长显著受阻,细胞增殖和伸长严重受损。此外,SSR1的突变还影响PIN蛋白的表达和定位,进而影响生长素的运输,导致根尖干细胞群落的维持受到干扰[3]。

在高浓度脯氨酸处理下,SSR1在维持线粒体电子传递链(Mitochondria Electron Transport Chain, mETC)功能和铁稳态中也发挥作用。研究显示,SSR1突变体对脯氨酸的敏感性增加,表现为线粒体活性氧(Mitochondrial Reactive Oxygen Species, ROS)水平升高、ATP含量降低、mETC复合物I和II活性下降以及铁含量减少。这些结果表明,SSR1在维持mETC的正常电子传递功能和铁稳态方面发挥着重要作用[4]。

在人类疾病中,SSR1也具有潜在的应用价值。研究发现,SSR1在多种癌症中表达上调,包括肝细胞癌(Hepatocellular Carcinoma, HCC)和肺腺癌。在HCC中,SSR1的表达水平与临床分期、病理分期和总生存期相关,表明SSR1可能成为HCC的潜在诊断和预后标志物[2,6]。此外,SSR1还与免疫细胞浸润相关,可能参与调节HCC的发生和发展[2]。

在肺动脉平滑肌细胞(Pulmonary Artery Smooth Muscle Cells, PASMCs)的焦亡过程中,circSSR1通过促进SSR1蛋白的翻译,激活内质网应激(Endoplasmic Reticulum Stress, ERS),进而导致PASMCs的焦亡。这一发现揭示了circSSR1在肺高压(Pulmonary Hypertension, PH)发病机制中的新调节机制,为PH的治疗提供了潜在靶点[5]。

综上所述,SSR1在多种生物学过程中发挥重要作用,包括蛋白质转运、心脏发育、植物根发育和生长素运输、线粒体功能和铁稳态、以及人类疾病的发生和发展。进一步研究SSR1的生物学功能和机制,有助于深入理解其参与的生物学过程,为相关疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Mesbah, K, Camus, A, Babinet, C, Barra, J. . Mutation in the Trapalpha/Ssr1 gene, encoding translocon-associated protein alpha, results in outflow tract morphogenetic defects. In Molecular and cellular biology, 26, 7760-71. doi:. https://pubmed.ncbi.nlm.nih.gov/17015483/
2. Xiao, Qingyu, Qu, Weixiang, Shen, Wenying, Cheng, Zhen, Wu, Haijun. 2024. Exploring SSR1 as a novel diagnostic and prognostic biomarker in hepatocellular carcinoma, and its relationship with immune infiltration. In Translational cancer research, 13, 5278-5299. doi:10.21037/tcr-24-277. https://pubmed.ncbi.nlm.nih.gov/39525035/
3. Zhang, Min, Wang, Cuiping, Lin, Qingfang, Zhao, Rongmin, Hua, Xuejun. 2015. A tetratricopeptide repeat domain-containing protein SSR1 located in mitochondria is involved in root development and auxin polar transport in Arabidopsis. In The Plant journal : for cell and molecular biology, 83, 582-99. doi:10.1111/tpj.12911. https://pubmed.ncbi.nlm.nih.gov/26072661/
4. Han, Hui Ling, Liu, Jie, Feng, Xuan Jun, Xu, Tao, Hua, Xue Jun. 2020. SSR1 is involved in maintaining the function of mitochondria electron transport chain and iron homeostasis upon proline treatment in Arabidopsis. In Journal of plant physiology, 256, 153325. doi:10.1016/j.jplph.2020.153325. https://pubmed.ncbi.nlm.nih.gov/33271443/
5. Guan, Xiaoyu, Du, Hongxia, Wang, Xiaoying, Yu, Hang, Zhu, Daling. 2024. CircSSR1 regulates pyroptosis of pulmonary artery smooth muscle cells through parental protein SSR1 mediating endoplasmic reticulum stress. In Respiratory research, 25, 355. doi:10.1186/s12931-024-02986-w. https://pubmed.ncbi.nlm.nih.gov/39354535/
6. Chen, Liang, Lin, Yunhua, Liu, Guoqing, Xie, Jiaheng, Yu, Hongzhu. 2021. Clinical Value for Diagnosis and Prognosis of Signal Sequence Receptor 1 (SSR1) and Its Potential Mechanism in Hepatocellular Carcinoma: A Comprehensive Study Based on High-Throughput Data Analysis. In International journal of general medicine, 14, 7435-7451. doi:10.2147/IJGM.S336725. https://pubmed.ncbi.nlm.nih.gov/34744454/