Psmd11-KO 基因敲除小鼠

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产品名称

Psmd11-KO 基因敲除小鼠

产品编号

S-KO-12938

品系全称

C57BL/6NCya-Psmd11em1/Cya

品系背景

C57BL/6NCya

品系编号

KOCMP-69077-Psmd11-B6N-VA

品系状态

使用本品系发表的文献需注明: Psmd11-KO 基因敲除小鼠 mice (Strain S-KO-12938) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量

基本信息

基因研究概述

质控标准

基因
基因全称
proteasome (prosome, macropain) 26S subunit, non-ATPase, 11
基因别称
1700089D09Rik,1810019E17Rik,2610024G20Rik,2810055C24Rik,P44.5,S9
染色体号
Chr 11 (Mouse)
转录本 ID
NCBI: NM_178616 | Ensembl: ENSMUST00000017572
修饰方式
全身性基因敲除
靶向范围
Exon 2~9
敲除长度
~33.4 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:1916327Homozygous null mice are embryonic lethal before E7.5. Heterozygous mice are growth retarded.
PSMD11,即26S蛋白酶非ATP酶调节亚基11,是蛋白酶体复合物中的一个重要组成部分。蛋白酶体是一种大型的多亚基蛋白复合物,负责维持细胞内蛋白质稳态,通过清除泛素标记的损伤、错误折叠或不必要的蛋白质。PSMD11在蛋白酶体功能中发挥着关键作用,包括调节胚胎干细胞蛋白酶体活性和ATP依赖性泛素化蛋白的降解[1]。此外,PSMD11还参与细胞存活、生长和发育等生物学过程[2]。

PSMD11的突变和表达异常与多种疾病相关。研究发现,PSMD11的缺失或突变会导致原发性蛋白酶体病,这是一种罕见的早发性神经发育障碍(NDD),表现为智力障碍、神经发育迟缓和反复肥胖等症状[3]。此外,PSMD11的表达异常还与肝细胞癌、肺腺癌和急性髓细胞白血病等恶性肿瘤的发生和进展相关[4,5,6,7,8,9,10]。

在肝细胞癌中,PSMD11的表达水平显著高于癌旁组织,并且与不良预后相关。PSMD11通过调节CDK4的泛素化降解来促进肝细胞癌的增殖[4]。在肺腺癌中,PSMD11的表达水平与预后相关,低表达患者预后较好。PSMD11的表达与髓源性抑制细胞浸润和免疫抑制分子表达增加相关,提示其在肺腺癌的免疫逃逸中发挥重要作用[5,8]。在急性髓细胞白血病中,PSMD11的表达水平与不良预后相关。PSMD11的表达与肿瘤免疫微环境相关,低表达患者免疫效应细胞浸润增加,对分子靶向药物敏感性提高[10]。

PSMD11的功能受到多种因素的调控。研究发现,PKA(cAMP依赖性蛋白激酶或蛋白激酶A)可以通过pS14-Rpn6(丝氨酸14磷酸化的Rpn6)激活26S蛋白酶体,从而减轻蛋白质毒性[6]。此外,PSMD11的表达还受到缺氧等环境因素的影响,与肿瘤免疫微环境和药物耐药性相关[10]。

综上所述,PSMD11是一种重要的蛋白酶体调节亚基,参与调节蛋白质稳态和细胞生物学过程。PSMD11的突变和表达异常与多种疾病相关,包括原发性蛋白酶体病和恶性肿瘤。PSMD11的功能受到多种因素的调控,包括PKA和缺氧等。深入研究PSMD11的生物学功能和调控机制,有助于揭示疾病的发生和发展机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Zhao, Linlin, Zhao, Jinming, Zhang, Yingying, Wang, Chuanxin, Qi, Tonggang. 2021. Generation and identification of a conditional knockout allele for the PSMD11 gene in mice. In BMC developmental biology, 21, 4. doi:10.1186/s12861-020-00233-1. https://pubmed.ncbi.nlm.nih.gov/33517884/
2. Deb, Wallid, Rosenfelt, Cory, Vignard, Virginie, Küry, Sébastien, Ebstein, Frédéric. 2024. PSMD11 loss-of-function variants correlate with a neurobehavioral phenotype, obesity, and increased interferon response. In American journal of human genetics, 111, 1352-1369. doi:10.1016/j.ajhg.2024.05.016. https://pubmed.ncbi.nlm.nih.gov/38866022/
3. Sun, Liang, Liu, Zitao, Wu, Zhengyi, Hu, Junwen, Yin, Xiangbao. 2024. PSMD11 promotes the proliferation of hepatocellular carcinoma by regulating the ubiquitination degradation of CDK4. In Cellular signalling, 121, 111279. doi:10.1016/j.cellsig.2024.111279. https://pubmed.ncbi.nlm.nih.gov/38944255/
4. Zhang, Cong, Xu, Tiantian, Ji, Kun, Jing, Li, Sun, Jun-Hui. 2023. An integrative analysis reveals the prognostic value and potential functions of PSMD11 in hepatocellular carcinoma. In Molecular carcinogenesis, 62, 1355-1368. doi:10.1002/mc.23568. https://pubmed.ncbi.nlm.nih.gov/37212487/
5. Huang, Qiumin, Tian, Ran, Yu, Jinxi, Du, Wei. . Identification of PSMD11 as a novel cuproptosis- and immune-related prognostic biomarker promoting lung adenocarcinoma progression. In Cancer medicine, 13, e7379. doi:10.1002/cam4.7379. https://pubmed.ncbi.nlm.nih.gov/38859698/
6. Yang, Liuqing, Parajuli, Nirmal, Wu, Penglong, Liu, Jinbao, Wang, Xuejun. 2023. S14-Phosphorylated RPN6 Mediates Proteasome Activation by PKA and Alleviates Proteinopathy. In Circulation research, 133, 572-587. doi:10.1161/CIRCRESAHA.123.322887. https://pubmed.ncbi.nlm.nih.gov/37641975/
7. Vafaee, Reza, Nikzamir, Abdolrahim, Razzaghi, Mohhamadreza, Ahmadzadeh, Alireza, Emamhadi, MohammadAli. 2020. An Investigation of Post-radiation Gene Expression Profiles: A System Biology Study. In Journal of lasers in medical sciences, 11, S101-S106. doi:10.34172/jlms.2020.S16. https://pubmed.ncbi.nlm.nih.gov/33995977/
8. Xi, Yong, Zeng, Jing, Zhou, Yundong, Rajandram, Retnagowri, Krishnasamy, Sivakumar. 2024. Prognostic value and potential biological function of PMSD11 in lung adenocarcinoma. In Journal of thoracic disease, 16, 7819-7835. doi:10.21037/jtd-24-1622. https://pubmed.ncbi.nlm.nih.gov/39678883/
9. Lintas, Carla, Sacco, Roberto, Tabolacci, Claudio, Baccarin, Marco, Persico, Antonio M. 2018. An Interstitial 17q11.2 de novo Deletion Involving the CDK5R1 Gene in a High-Functioning Autistic Patient. In Molecular syndromology, 9, 247-252. doi:10.1159/000491802. https://pubmed.ncbi.nlm.nih.gov/30733659/
10. Liu, Xin, Wang, Li, Kang, Qian, Feng, Cheng, Wang, Jishi. 2024. A hypoxia-related genes prognostic risk model, and mechanisms of hypoxia contributing to poor prognosis through immune microenvironment and drug resistance in acute myeloid leukemia. In Frontiers in pharmacology, 15, 1339465. doi:10.3389/fphar.2024.1339465. https://pubmed.ncbi.nlm.nih.gov/38482057/