Pin1-KO 基因敲除小鼠

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产品名称

Pin1-KO 基因敲除小鼠

产品编号

S-KO-07131

品系全称

C57BL/6JCya-Pin1em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-23988-Pin1-B6J-VA

品系状态

使用本品系发表的文献需注明: Pin1-KO 基因敲除小鼠 mice (Strain S-KO-07131) 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
peptidyl-prolyl cis/trans isomerase, NIMA-interacting 1
基因别称
0610025L01Rik,D9Bwg1161e
染色体号
Chr 9 (Mouse)
转录本 ID
NCBI: NM_023371 | Ensembl: ENSMUST00000034689
修饰方式
全身性基因敲除
靶向范围
Exon 1~2
敲除长度
~3.8 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:1346036Homozygotes exhibit cell-proliferation abnormalities, including a late-developing reduction in body weight and progressive testicular and retinal atrophies. Mutant females fail to undergo mammary epithelial duct expansion associated with pregnancy.
Pin1,也称为肽基脯氨酰顺反异构酶,是一种重要的蛋白质,它在细胞内发挥多种生物学功能。Pin1是一种特异性结合到磷酸化的丝氨酸或苏氨酸残基 preceding a proline (pSer/Thr-Pro) motif的蛋白质,并催化脯氨酸亚氨基肽键的顺反异构化,导致其底物的构象变化。Pin1调节许多生物过程,并参与人类疾病的发展,如癌症和神经性疾病[2]。

Pin1在多种癌症中过度表达,如胰腺癌、肝癌和结直肠癌。在胰腺癌中,Pin1在癌细胞和癌症相关成纤维细胞(CAFs)中均过度表达,并与PDAC患者的预后不良相关。使用临床可用的药物靶向Pin1可以诱导侵袭性PDAC的完全消除或持续缓解,与抗PD-1和吉西他滨协同作用[1]。在肝癌中,Pin1的表达与TP53基因状态相关。PIN1在TP53野生型肝癌细胞中的沉默导致肿瘤细胞增殖,而PIN1在含有突变TP53的肝癌细胞中的沉默显著降低了细胞增殖、迁移和侵袭[5]。在结直肠癌中,PIN1的表达与β-连环蛋白基因突变/表达相关,PIN1基因过表达与HCC的发生有关[6]。

Pin1还在阿尔茨海默病(AD)的发展中发挥重要作用。Pin1在女性AD患者中的表达降低,与认知和神经病理表型相关。Pin1是tau磷酸化信号通路的关键调节因子,当Pin1基因被删除时,会导致tau和Aβ相关的病理改变[3]。Pin1基因启动子的甲基化与AD的风险相关,Pin1基因表达和甲基化在AD患者中均降低,但在女性AD患者中,Pin1表达的变化早于临床症状的出现,并与AD风险相关的早期事件相关[4]。

此外,Pin1还参与其他疾病的发展,如慢性肾脏疾病(CKD)和高血压。Pin1基因启动子中的单核苷酸多态性(SNP)与CKD继发性甲状旁腺功能亢进(SHPT)的风险相关[7]。BRD4和PIN1基因多态性与高血压患者的高脉压风险相关[8]。Pin1还参与肿瘤微环境中的代谢串扰,调节肿瘤细胞的代谢和与微环境的相互作用[9]。

综上所述,Pin1是一种重要的蛋白质,参与多种生物学过程,并在多种疾病中发挥重要作用。Pin1在癌症、AD、CKD和高血压等疾病的发展中发挥关键作用,可能是治疗这些疾病的新靶点。此外,Pin1还参与肿瘤微环境中的代谢串扰,调节肿瘤细胞的代谢和与微环境的相互作用,为肿瘤的治疗提供了新的思路。

参考文献:
1. Koikawa, Kazuhiro, Kibe, Shin, Suizu, Futoshi, Zhou, Xiao Zhen, Lu, Kun Ping. 2021. Targeting Pin1 renders pancreatic cancer eradicable by synergizing with immunochemotherapy. In Cell, 184, 4753-4771.e27. doi:10.1016/j.cell.2021.07.020. https://pubmed.ncbi.nlm.nih.gov/34388391/
2. Hu, Xiangming, Chen, Lin-Feng. 2020. Pinning Down the Transcription: A Role for Peptidyl-Prolyl cis-trans Isomerase Pin1 in Gene Expression. In Frontiers in cell and developmental biology, 8, 179. doi:10.3389/fcell.2020.00179. https://pubmed.ncbi.nlm.nih.gov/32266261/
3. de Ávila, Camila, Suazo, Crystal, Nolz, Jennifer, Readhead, Benjamin, Mastroeni, Diego. 2023. Reduced PIN1 gene expression in neocortical and limbic brain regions in female Alzheimer's patients correlates with cognitive and neuropathological phenotypes. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.08.14.553279. https://pubmed.ncbi.nlm.nih.gov/37645898/
4. Ma, Suk L, Tang, Nelson L S, Lam, Linda C Wa. . Promoter Methylation and Gene Expression of Pin1 Associated with the Risk of Alzheimer's Disease in Southern Chinese. In Current Alzheimer research, 17, 1232-1237. doi:10.2174/1567205018666210208163946. https://pubmed.ncbi.nlm.nih.gov/33557736/
5. Bae, Jun Sang, Noh, Sang Jae, Kim, Kyoung Min, Park, Byung-Hyun, Moon, Woo Sung. 2016. PIN1 in hepatocellular carcinoma is associated with TP53 gene status. In Oncology reports, 36, 2405-11. doi:10.3892/or.2016.5001. https://pubmed.ncbi.nlm.nih.gov/27499097/
6. Wang, Hui, Zhang, Jinxiang, Feng, Wei, Zheng, Qichang, Li, Zhuoya. . PIN1 gene overexpression and beta-catenin gene mutation/expression in hepatocellular carcinoma and their significance. In Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban, 27, 54-7. doi:. https://pubmed.ncbi.nlm.nih.gov/17393110/
7. Zhao, Yu, Zhang, Li-Li, Ding, Fa-Xian, Qi, Yuan-Yuan, Wang, Jing. 2016. Pin1 and secondary hyperparathyroidism of chronic kidney disease: gene polymorphisms and protein levels. In Renal failure, 39, 159-165. doi:10.1080/0886022X.2016.1256310. https://pubmed.ncbi.nlm.nih.gov/27876426/
8. Qiu, Jin-Jia, Yang, Rui-Zhi, Tang, Yi-Jie, Zeng, Kai, Wu, Xiao-Dan. 2020. BRD4 and PIN1 gene polymorphisms are associated with high pulse pressure risk in a southeastern Chinese population. In BMC cardiovascular disorders, 20, 475. doi:10.1186/s12872-020-01757-x. https://pubmed.ncbi.nlm.nih.gov/33148187/
9. Caligiuri, Isabella, Vincenzo, Canzonieri, Asano, Tomochiro, Kumar, Vinit, Rizzolio, Flavio. 2023. The metabolic crosstalk between PIN1 and the tumour microenvironment. In Seminars in cancer biology, 91, 143-157. doi:10.1016/j.semcancer.2023.03.001. https://pubmed.ncbi.nlm.nih.gov/36871635/