Vps33b-KO 基因敲除小鼠

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产品名称

Vps33b-KO 基因敲除小鼠

产品编号

S-KO-17539

品系全称

C57BL/6JCya-Vps33bem1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-233405-Vps33b-B6J-VB

品系状态

使用本品系发表的文献需注明: Vps33b-KO 基因敲除小鼠 mice (Strain S-KO-17539) 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
vacuolar protein sorting 33B
基因别称
-
染色体号
Chr 7 (Mouse)
转录本 ID
NCBI: NM_178070 | Ensembl: ENSMUST00000032749
修饰方式
全身性基因敲除
靶向范围
Exon 2~3
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:2446237Mice homozygous for a conditional allele activated by an inducible cre exhibit dry scaly skin, hair loss, thrombocytosis, abnormal alpha-granule development, extramedullary hematopoiesis, abnormal platelets and megakaryocytes, and defects in tail tendon collagen I structure.
VPS33B,也称为Vacuolar protein sorting 33B,是一种编码参与细胞内蛋白质分选和囊泡转运的蛋白质的基因。VPS33B位于染色体15q26.1上,其编码的蛋白质在多种生物学过程中发挥重要作用,包括细胞内囊泡转运、膜蛋白定位、细胞极性维持和信号转导。VPS33B的突变与多种疾病相关,其中最著名的是关节挛缩-肾功能障碍-胆汁淤积综合征(ARCS1)[1,2,3,4,5,6,7,8]。

ARCS1是一种罕见的常染色体隐性遗传病,主要特征是先天性关节挛缩、肾功能障碍和新生儿胆汁淤积。VPS33B突变导致的ARCS1患者通常在出生后2年内死亡,但也有少数患者表现出较轻的临床症状并存活时间较长[1,2]。除了ARCS1,VPS33B突变还与其他疾病相关,如胆汁淤积和肾功能不全[3]。此外,VPS33B突变还与血浆血管性血友病因子(VWF)水平降低相关[4]。

VPS33B的突变导致其编码的蛋白质功能受损,进而影响细胞内囊泡转运和膜蛋白定位。VPS33B蛋白与RAB11A相互作用,参与循环内体上的膜蛋白转运。VPS33B突变导致ATP结合盒转运蛋白在细胞膜上的错位,从而影响胆汁酸和溶质的转运[7]。此外,VPS33B突变还导致肝细胞极性丧失和胆管发育异常[7,9]。

研究VPS33B突变导致ARCS1的分子机制对于开发针对该疾病的治疗方法具有重要意义。目前,基因治疗被认为是治疗ARCS1最有希望的策略之一。通过将正常的VPS33B基因导入患者体内,可以恢复VPS33B蛋白的功能,从而改善患者的临床症状[7]。此外,研究VPS33B突变导致的细胞内囊泡转运和膜蛋白定位异常,可以为开发新的治疗方法提供理论依据。

总之,VPS33B是一种重要的基因,其突变与多种疾病相关。深入研究VPS33B的生物学功能和突变导致的疾病机制,对于开发针对这些疾病的治疗方法具有重要意义。基因治疗和其他治疗方法的研究有望为ARCS1和其他VPS33B突变相关疾病的患者带来新的希望。

参考文献:
1. Yang, Hui, Lin, Shuang-Zhu, Guan, Shi-Hui, Yang, Gui-Dan, Zhang, Su-Li. . Two novel mutations in the VPS33B gene in a Chinese patient with arthrogryposis, renal dysfunction and cholestasis syndrome 1: A case report. In World journal of clinical cases, 10, 11016-11022. doi:10.12998/wjcc.v10.i30.11016. https://pubmed.ncbi.nlm.nih.gov/36338198/
2. Zhu, Yingjie, Chen, Dongmei. 2022. Two novel mutations in VPS33B gene cause a milder ARC syndrome with prolonged survival in a 12-year-old patient: Case report. In Frontiers in pediatrics, 10, 1041080. doi:10.3389/fped.2022.1041080. https://pubmed.ncbi.nlm.nih.gov/36568436/
3. Ma, S Q, Bai, X, Cao, L J, Yu, Z J, Jiang, M. . [Rare VPS33B gene mutation combined with GP1BA mutation causes severe decrease in plasma VWF levels: a case report and literature review]. In Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi, 45, 602-605. doi:10.3760/cma.j.cn121090-20231216-00317. https://pubmed.ncbi.nlm.nih.gov/39134495/
4. Agakidou, Eleni, Agakidis, Charalampos, Kambouris, Marios, Gerou, Spyridon, Sarafidis, Kosmas. 2020. A Novel Mutation of VPS33B Gene Associated with Incomplete Arthrogryposis-Renal Dysfunction-Cholestasis Phenotype. In Case reports in genetics, 2020, 8872294. doi:10.1155/2020/8872294. https://pubmed.ncbi.nlm.nih.gov/33029437/
5. Mutlu, Mehmet, Aslan, Yakup, Aktürk-Acar, Filiz, Erduran, Erol, Kalyoncu, Mukaddes. . ARC syndrome. In The Turkish journal of pediatrics, 59, 487-490. doi:10.24953/turkjped.2017.04.019. https://pubmed.ncbi.nlm.nih.gov/29624233/
6. Del Brío Castillo, Rodrigo, Squires, James E, McKiernan, Patrick J. 2019. A novel mutation in VPS33B gene causing a milder ARC syndrome phenotype with prolonged survival. In JIMD reports, 47, 4-8. doi:10.1002/jmd2.12027. https://pubmed.ncbi.nlm.nih.gov/31240160/
7. Hanley, Joanna, Dhar, Dipok Kumar, Mazzacuva, Francesca, Clayton, Peter, Gissen, Paul. 2017. Vps33b is crucial for structural and functional hepatocyte polarity. In Journal of hepatology, 66, 1001-1011. doi:10.1016/j.jhep.2017.01.001. https://pubmed.ncbi.nlm.nih.gov/28082148/
8. Megarbane, Andre, Bizzari, Sami, Deepthi, Asha, Delague, Valérie, Urtizberea, J Andoni. . A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort. In Journal of neuromuscular diseases, 9, 193-210. doi:10.3233/JND-210652. https://pubmed.ncbi.nlm.nih.gov/34602496/
9. Matthews, Randolph P, Plumb-Rudewiez, Nicolas, Lorent, Kristin, Lemaigre, Frederic, Pack, Michael. . Zebrafish vps33b, an ortholog of the gene responsible for human arthrogryposis-renal dysfunction-cholestasis syndrome, regulates biliary development downstream of the onecut transcription factor hnf6. In Development (Cambridge, England), 132, 5295-306. doi:. https://pubmed.ncbi.nlm.nih.gov/16284120/