Gp6-KO 基因敲除小鼠

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产品名称

Gp6-KO 基因敲除小鼠

产品编号

S-KO-20139

品系全称

C57BL/6JCya-Gp6em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-243816-Gp6-B6J-VA

品系状态

使用本品系发表的文献需注明: Gp6-KO 基因敲除小鼠 mice (Strain S-KO-20139) 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
glycoprotein 6 platelet
基因别称
9830166G18Rik,Gm469,Gpvi
染色体号
Chr 7 (Mouse)
转录本 ID
NCBI: NM_001163014 | Ensembl: ENSMUST00000206928
修饰方式
全身性基因敲除
靶向范围
Exon 1~3
敲除长度
~5.2 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:1889810Mice homozygous with disruptions in this gene display functional abnormalities in their platelets including failure of the platelets to aggregate and to become activated. The effects on blood clotting are minor however.
GP6(Glycoprotein VI)是一种重要的血小板膜糖蛋白,编码GPVI。GPVI是胶原的关键血小板受体,对于适当的血小板活化、粘附和聚集至关重要。GP6基因的表达受到多种转录因子的调控,包括GATA-1、Sp1和Fli-1,以及CpG位点的甲基化状态。GP6基因的变异与多种疾病相关,包括粘性血小板综合征(SPS)、复发性流产、深静脉血栓形成(DVT)和/或肺栓塞,以及非致命性心肌梗死(AMI)。

在粘性血小板综合征(SPS)中,GP6基因的变异与血小板高聚集性有关。研究发现,SPS患者中GP6基因的多个单核苷酸多态性(SNPs)的频率高于对照组,包括rs1671152、rs1654433、rs1613662、rs1654419和rs2304167[1,2,4,7]。此外,haplotype分析也显示,SPS患者中某些haplotypes(如ACGG、CCGT、CTGAG和CGATAG)的频率显著高于对照组[1,2,4,7]。这些研究结果支持了GP6基因变异可能与血小板高聚集性有关,而血小板高聚集性可能是复发性流产的原因之一。

GP6基因的变异也与深静脉血栓形成(DVT)和/或肺栓塞有关。研究发现,SPS患者中GP6基因的多个SNPs(如rs1654410、rs1671153、rs1654419、rs11669150、rs12610286、rs1654431和rs1613662)与DVT和/或肺栓塞的发病风险增加相关[3]。此外,研究发现,GP6基因的某些SNPs(如rs1671153和rs1654419)与男性患者中SPS的发病风险增加相关[3]。

GP6基因的变异还与非致命性心肌梗死(AMI)有关。研究发现,GP6基因的某些SNPs(如rs1163662)与非致命性AMI的发病风险降低相关[5]。此外,研究发现,GP6基因的某些haplotypes(如G-T-G-G、T-C-A-A、G-C-G-A和G-T-A-A)与复发性流产的发病风险增加相关[6]。

综上所述,GP6基因的变异与多种疾病相关,包括粘性血小板综合征(SPS)、复发性流产、深静脉血栓形成(DVT)和/或肺栓塞,以及非致命性心肌梗死(AMI)。这些研究结果支持了GP6基因变异在血小板功能和血栓形成中的重要作用,并为相关疾病的治疗和预防提供了新的思路和策略。

参考文献:
1. Sokol, Juraj, Skerenova, Maria, Biringer, Kamil, Stasko, Jan, Kubisz, Peter. 2015. Genetic variations of the GP6 regulatory region in patients with sticky platelet syndrome and miscarriage. In Expert review of hematology, 8, 863-8. doi:10.1586/17474086.2015.1083417. https://pubmed.ncbi.nlm.nih.gov/26308704/
2. Sokol, Juraj, Biringer, Kamil, Skerenova, Maria, Danko, Jan, Kubisz, Peter. 2012. Platelet aggregation abnormalities in patients with fetal losses: the GP6 gene polymorphism. In Fertility and sterility, 98, 1170-4. doi:10.1016/j.fertnstert.2012.07.1108. https://pubmed.ncbi.nlm.nih.gov/22901851/
3. Kotuličová, Daniela, Chudý, Peter, Škereňová, Mária, Dobrotová, Miroslava, Kubisz, Peter. . Variability of GP6 gene in patients with sticky platelet syndrome and deep venous thrombosis and/or pulmonary embolism. In Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, 23, 543-7. doi:10.1097/MBC.0b013e328355a808. https://pubmed.ncbi.nlm.nih.gov/22821001/
4. Škereňová, Mária, Sokol, Juraj, Biringer, Kamil, Kubisz, Peter, Lasabová, Zora. 2017. GP6 Haplotype of Missense Variants is Associated with Sticky Platelet Syndrome Manifested by Fetal Loss. In Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 24, 63-69. doi:10.1177/1076029616685428. https://pubmed.ncbi.nlm.nih.gov/28041267/
5. Shaffer, J R, Kammerer, C M, Dorn, J, Trevisan, M, Donahue, R P. 2010. Polymorphisms in the platelet-specific collagen receptor GP6 are associated with risk of nonfatal myocardial infarction in Caucasians. In Nutrition, metabolism, and cardiovascular diseases : NMCD, 21, 546-52. doi:10.1016/j.numecd.2009.12.002. https://pubmed.ncbi.nlm.nih.gov/20227257/
6. Siddesh, Anjurani, Parveen, Farah, Misra, Maneesh Kumar, Phadke, Shubha R, Agrawal, Suraksha. 2014. Platelet-specific collagen receptor glycoprotein VI gene variants affect recurrent pregnancy loss. In Fertility and sterility, 102, 1078-1084.e3. doi:10.1016/j.fertnstert.2014.07.002. https://pubmed.ncbi.nlm.nih.gov/25086789/
7. Sokol, Juraj, Skerenova, Maria, Biringer, Kamil, Kubisz, Peter, Stasko, Jan. 2018. Glycoprotein VI Gene Variants Affect Pregnancy Loss in Patients With Platelet Hyperaggregability. In Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 24, 202S-208S. doi:10.1177/1076029618802358. https://pubmed.ncbi.nlm.nih.gov/30278775/