Ppp4r3a-KO 基因敲除小鼠

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产品名称

Ppp4r3a-KO 基因敲除小鼠

产品编号

S-KO-12818

品系全称

C57BL/6JCya-Ppp4r3aem1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-68734-Ppp4r3a-B6J-VA

品系状态

使用本品系发表的文献需注明: Ppp4r3a-KO 基因敲除小鼠 mice (Strain S-KO-12818) 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
protein phosphatase 4 regulatory subunit 3A
基因别称
1110034C04Rik,Smek1,mKIAA2010
染色体号
Chr 12 (Mouse)
转录本 ID
NCBI: NM_001160214 | Ensembl: ENSMUST00000163095
修饰方式
全身性基因敲除
靶向范围
Exon 4~10
敲除长度
~9.3 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:1915984Mice homozygous for a conditional allele exhibit increased anxiety- and depression-related behaviors with decreased miniature excitatory postsynaptic currents, decreased glutamate release, and decreased dendritic spine density.
Ppp4r3a,也称为Smek1,是蛋白磷酸酶4(PP4)的调节亚基,在多种生物学过程中发挥重要作用。PP4是一种广泛存在于真核细胞中的丝氨酸/苏氨酸蛋白磷酸酶,参与细胞周期的调控、信号转导、DNA损伤修复和细胞凋亡等多种生物学过程。Smek1与PP4的催化亚基PP4c结合,形成PP4全酶,共同参与这些生物学过程的调控。

Smek1在多种疾病中发挥重要作用,包括阿尔茨海默病(AD)、非髓性甲状腺癌(FNMTC)、肥胖、自身免疫性脑脊髓炎(EAE)、胃癌和白血病。在AD中,Smek1的变异与葡萄糖代谢下降相关,可能具有保护作用,可作为AD治疗的新靶点[1]。在FNMTC中,Smek1的错义突变可能导致肿瘤抑制功能的丧失,促进细胞增殖和迁移[2]。在肥胖中,Smek1的缺失可能促进葡萄糖摄取,改善肥胖相关的代谢功能障碍[3]。在EAE中,Smek1的缺失可能加剧实验性自身免疫性脑脊髓炎的病情,通过激活促炎小胶质细胞和抑制IDO1-AhR通路[4]。在胃癌中,Smek1可能通过调节基因表达影响肿瘤微环境和预后[5]。在白血病中,Smek1可能通过调节MAPK3、AKT、JAK/STAT、NFκB和TGFβ信号通路影响白血病细胞的生长和凋亡[8]。

此外,Smek1还参与胚胎干细胞(ESC)的分化过程。在ESC中,Wnt信号通路参与细胞命运决定,而Smek1通过促进组蛋白脱乙酰化来抑制Wnt靶基因brachyury的转录,从而维持ESC的多能性[6]。在皮质神经发生过程中,Smek1与Ryk-ICD结合,调节其核定位和功能,共同介导神经细胞命运的决定[7]。

综上所述,Ppp4r3a(Smek1)是一种重要的PP4调节亚基,参与细胞周期的调控、信号转导、DNA损伤修复和细胞凋亡等多种生物学过程。Smek1在多种疾病中发挥重要作用,包括阿尔茨海默病、非髓性甲状腺癌、肥胖、自身免疫性脑脊髓炎、胃癌和白血病。此外,Smek1还参与胚胎干细胞的多能性维持和皮质神经发生过程。Smek1的研究有助于深入理解PP4信号通路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。

参考文献:
1. Christopher, Leigh, Napolioni, Valerio, Khan, Raiyan R, Han, Summer S, Greicius, Michael D. 2017. A variant in PPP4R3A protects against alzheimer-related metabolic decline. In Annals of neurology, 82, 900-911. doi:10.1002/ana.25094. https://pubmed.ncbi.nlm.nih.gov/29130521/
2. Hu, Yixuan, Han, Zhuojun, Guo, Honghao, Jiang, Yujia, Huang, Tao. 2024. Identification of a Novel Germline PPP4R3A Missense Mutation Asp409Asn on Familial Non-Medullary Thyroid Carcinoma. In Biomedicines, 12, . doi:10.3390/biomedicines12010244. https://pubmed.ncbi.nlm.nih.gov/38275415/
3. Wei, Shijun, Song, Yu, Li, Zhengbin, Li, Jiangxia, Liu, Qiji. 2024. SMEK1 ablation promotes glucose uptake and improves obesity-related metabolic dysfunction via AMPK signaling pathway. In American journal of physiology. Endocrinology and metabolism, 326, E776-E790. doi:10.1152/ajpendo.00387.2023. https://pubmed.ncbi.nlm.nih.gov/38568153/
4. Dang, Dong, Zhang, Lilian, Gao, Lutao, Chen, Jian, Yang, Linnan. 2024. Analysis of genomic copy number variations through whole-genome scan in Yunling cattle. In Frontiers in veterinary science, 11, 1413504. doi:10.3389/fvets.2024.1413504. https://pubmed.ncbi.nlm.nih.gov/39104544/
5. Chen, Wenliang, Wang, Huanhuan, Achi, Ntiak, Gong, Rui, Zhao, Qiang. . Bioinformatics Analysis of the Expression and Prognostic Significance of Transcription Factor YY1 in Gastric Cancer. In Cancer reports (Hoboken, N.J.), 8, e70181. doi:10.1002/cnr2.70181. https://pubmed.ncbi.nlm.nih.gov/40088083/
6. Lyu, Jungmook, Jho, Eek-Hoon, Lu, Wange. 2011. Smek promotes histone deacetylation to suppress transcription of Wnt target gene brachyury in pluripotent embryonic stem cells. In Cell research, 21, 911-21. doi:10.1038/cr.2011.47. https://pubmed.ncbi.nlm.nih.gov/21423269/
7. Chang, Wen-Hsuan, Choi, Si Ho, Moon, Byoung-San, Weiner, Leslie P, Lu, Wange. 2017. Smek1/2 is a nuclear chaperone and cofactor for cleaved Wnt receptor Ryk, regulating cortical neurogenesis. In Proceedings of the National Academy of Sciences of the United States of America, 114, E10717-E10725. doi:10.1073/pnas.1715772114. https://pubmed.ncbi.nlm.nih.gov/29180410/
8. Kavousi, Nadieh, Tonge, Daniel P, Mourtada-Maarabouni, Mirna. 2023. New insights into the functional role of protein phosphatase 4 regulatory subunit PP4R3A/SMEK1 in the regulation of leukemic cell fate. In International journal of biological macromolecules, 233, 123467. doi:10.1016/j.ijbiomac.2023.123467. https://pubmed.ncbi.nlm.nih.gov/36731689/