Nck2-KO 基因敲除小鼠

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产品名称

Nck2-KO 基因敲除小鼠

产品编号

S-KO-03337

品系全称

C57BL/6JCya-Nck2em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-17974-Nck2-B6J-VA

品系状态

使用本品系发表的文献需注明: Nck2-KO 基因敲除小鼠 mice (Strain S-KO-03337) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
KO小鼠库模型
ErbB信号通路

基本信息

基因研究概述

质控标准

基因
基因全称
non-catalytic region of tyrosine kinase adaptor protein 2
基因别称
4833426I10Rik,Grb4,NCKbeta,Nck-2
染色体号
Chr 1 (Mouse)
转录本 ID
NCBI: NM_010879 | Ensembl: ENSMUST00000086421
修饰方式
全身性基因敲除
靶向范围
Exon 4
敲除长度
~1.3 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:1306821Mice homozygous for disruption of this gene display no abnormal phenotype.
Nck2(非受体酪氨酸激酶连接蛋白2)是一种重要的信号转导适配蛋白,属于Nck家族成员。Nck家族由Nck1和Nck2两个同源蛋白组成,它们在细胞信号传导中发挥着重要作用,特别是在细胞增殖、迁移、粘附和细胞骨架动力学等方面[4]。Nck2蛋白具有一个SRC同源2(SH2)结构域和三个SH3结构域,这些结构域使其能够与多种蛋白质相互作用,从而调节信号通路和细胞功能。

Nck2在多种疾病中发挥着重要作用,包括阿尔茨海默病(AD)、乳腺癌、正常张力性青光眼和药物依赖等。研究表明,Nck2基因的多态性与AD的风险相关[1]。此外,Nck2在AD患者中表现出细胞特异性效应,例如在神经元中发挥作用[2]。在乳腺癌中,Nck2的表达与乳腺发育和形态发生密切相关,Nck2的失调可能促进乳腺癌的进展和转移[3]。此外,Nck2基因的多态性与正常张力性青光眼的风险相关[5][6][9][10]。最近的研究还发现,Nck2基因与药物依赖相关,特别是与阿片类药物的依赖性有关[7]。

Nck2在肾脏滤过屏障的维持中也发挥着重要作用。研究表明,Nck1/2信号通路在足细胞中控制着α肌动蛋白-4介导的肌动蛋白组织、粘附和基底膜组成[8]。Nck1/2的复合缺失改变了与肌动蛋白结合、细胞粘附和细胞外基质组成相关的基因表达,导致细胞粘附缺陷和基底膜形态改变。这些发现揭示了Nck蛋白在调节足细胞粘附、控制基底膜组成和维持滤过屏障完整性方面的独特而互补的作用。

综上所述,Nck2是一种重要的信号转导适配蛋白,参与多种生物学过程和疾病的发生。Nck2在细胞增殖、迁移、粘附、细胞骨架动力学和肾脏滤过屏障维持等方面发挥着重要作用。Nck2的失调与多种疾病相关,包括阿尔茨海默病、乳腺癌、正常张力性青光眼和药物依赖等。进一步研究Nck2的生物学功能和疾病发生机制,有助于深入了解细胞信号传导的复杂性和疾病的治疗策略。

参考文献:
1. Schwartzentruber, Jeremy, Cooper, Sarah, Liu, Jimmy Z, Beltrao, Pedro, Bassett, Andrew. 2021. Genome-wide meta-analysis, fine-mapping and integrative prioritization implicate new Alzheimer's disease risk genes. In Nature genetics, 53, 392-402. doi:10.1038/s41588-020-00776-w. https://pubmed.ncbi.nlm.nih.gov/33589840/
2. Brase, Logan, You, Shih-Feng, D'Oliveira Albanus, Ricardo, Benitez, Bruno A, Harari, Oscar. 2023. Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers. In Nature communications, 14, 2314. doi:10.1038/s41467-023-37437-5. https://pubmed.ncbi.nlm.nih.gov/37085492/
3. Golding, Adam P, Ferrier, Benjamin, New, Laura A, Moorehead, Roger A, Jones, Nina. 2023. Distinct Requirements for Adaptor Proteins NCK1 and NCK2 in Mammary Gland Development. In Journal of mammary gland biology and neoplasia, 28, 19. doi:10.1007/s10911-023-09541-1. https://pubmed.ncbi.nlm.nih.gov/37479911/
4. Teyssier, Valentine, Williamson, Casey R, Shata, Erka, Jones, Nina, Bisson, Nicolas. . Adapting to change: resolving the dynamic and dual roles of NCK1 and NCK2. In The Biochemical journal, 481, 1411-1435. doi:10.1042/BCJ20230232. https://pubmed.ncbi.nlm.nih.gov/39392452/
5. Liu, Zhifa, Guo, Xiaobo, Jiang, Yuan, Zhang, Heping. 2013. NCK2 is significantly associated with opiates addiction in African-origin men. In TheScientificWorldJournal, 2013, 748979. doi:10.1155/2013/748979. https://pubmed.ncbi.nlm.nih.gov/23533358/
6. Jung, Seung-Hyun, Lee, Young Chun, Lee, Mee Yon, Shin, Hye-Young. 2019. Association of HK2 and NCK2 with normal-tension glaucoma in a population from the Republic of Korea. In Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 257, 2717-2721. doi:10.1007/s00417-019-04467-z. https://pubmed.ncbi.nlm.nih.gov/31512042/
7. Martin, Claire E, Phippen, Noah J, Keyvani Chahi, Ava, Gingras, Anne-Claude, Jones, Nina. . Complementary Nck1/2 Signaling in Podocytes Controls α Actinin-4-Mediated Actin Organization, Adhesion, and Basement Membrane Composition. In Journal of the American Society of Nephrology : JASN, 33, 1546-1567. doi:10.1681/ASN.2021101343. https://pubmed.ncbi.nlm.nih.gov/35906089/
8. Zhang, Min, Zhou, Huan, Liu, Dan, Yu, Ruoying, Chen, Jun. 2020. A Case of Lung Adenocarcinoma Harboring a Rare LOC285000-ALK-NCK2 Gene Fusion Identified by Next-Generation Sequencing With Long-Term Response to Crizotinib. In JTO clinical and research reports, 2, 100106. doi:10.1016/j.jtocrr.2020.100106. https://pubmed.ncbi.nlm.nih.gov/34589983/
9. Pan, Lijie, Wu, Jian, Wang, Ningli. 2024. Association of Gene Polymorphisms with Normal Tension Glaucoma: A Systematic Review and Meta-Analysis. In Genes, 15, . doi:10.3390/genes15040491. https://pubmed.ncbi.nlm.nih.gov/38674425/
10. Shi, Dong, Funayama, Tomoyo, Mashima, Yukihiko, Richards, Julia E, Fuse, Nobuo. 2013. Association of HK2 and NCK2 with normal tension glaucoma in the Japanese population. In PloS one, 8, e54115. doi:10.1371/journal.pone.0054115. https://pubmed.ncbi.nlm.nih.gov/23349798/