Tbc1d23-KO 基因敲除小鼠

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产品名称

Tbc1d23-KO 基因敲除小鼠

产品编号

S-KO-12347

品系全称

C57BL/6JCya-Tbc1d23em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-67581-Tbc1d23-B6J-VA

品系状态

使用本品系发表的文献需注明: Tbc1d23-KO 基因敲除小鼠 mice (Strain S-KO-12347) 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
TBC1 domain family, member 23
基因别称
4930451A13Rik,D030022P07Rik
染色体号
Chr 16 (Mouse)
转录本 ID
NCBI: NM_026254 | Ensembl: ENSMUST00000023431
修饰方式
全身性基因敲除
靶向范围
Exon 3
敲除长度
~1.5 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:1914831Mice homozygous for a gene trapped allele exhibit increased serum cytokine production and inflammatory cells in the peritoneum following i.p. lipopolysaccharide injection.
Tbc1d23基因,也称为Tre2-Bub2-Cdc16(TBC)结构域家族成员23,是一种编码RAB-GAP(RAB特异性GTPase活化蛋白)的基因。RAB-GAPs是一类负调节RAB蛋白的蛋白质,RAB蛋白是一类小GTP酶,在细胞内的囊泡转运和膜融合过程中发挥重要作用。Tbc1d23基因的突变与多种疾病相关,包括Pontocerebellar hypoplasia(PCH,小脑发育不良)和某些癌症[1][2][3][4][5][6][7][8][9][10]。

PCH是一种罕见的神经发育障碍,特征是脑桥和小脑的发育不良。Tbc1d23基因的突变已被证明是PCH的一种遗传原因[1][4][5][8]。Tbc1d23基因在细胞内的定位是在高尔基体的反面,并且受小GTP酶Arl1和Arl8的调节,这表明它可能参与高尔基体膜转运的过程[4]。此外,Tbc1d23基因的突变还可能影响皮质发育,导致智力障碍和头围减小[5]。

除了与PCH相关,Tbc1d23基因还与非小细胞肺癌(NSCLC)的预后不良相关[2]。研究发现,Tbc1d23基因与Ras相关的蛋白质Rab-11A相互作用,通过β1整合素促进NSCLC的进展。Tbc1d23基因的表达与肿瘤大小、分化程度、转移、TNM分期和预后不良相关[2]。

Tbc1d23基因还与先天免疫信号传导的抑制有关[3]。研究发现,Tbc1d23基因是先天免疫信号传导的一般抑制剂,能够强烈抑制多种TLR和Dectin信号通路。Tbc1d23基因可能通过作为RAB-GAP来调节先天免疫信号传导[3]。

综上所述,Tbc1d23基因是一种编码RAB-GAP的基因,其突变与PCH和NSCLC等疾病相关。Tbc1d23基因在细胞内的定位是在高尔基体的反面,并且可能参与高尔基体膜转运的过程。此外,Tbc1d23基因还与先天免疫信号传导的抑制有关。研究Tbc1d23基因的功能和作用机制有助于深入理解其与疾病的关系,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Zhao, Lin, Deng, Huaqing, Yang, Qing, Billadeau, Daniel D, Jia, Da. 2023. FAM91A1-TBC1D23 complex structure reveals human genetic variations susceptible for PCH. In Proceedings of the National Academy of Sciences of the United States of America, 120, e2309910120. doi:10.1073/pnas.2309910120. https://pubmed.ncbi.nlm.nih.gov/37903274/
2. Zhang, Yao, Su, Hongbo, Wudu, Muli, Zou, Zifang, Qiu, Xueshan. 2021. TBC1 domain family member 23 interacts with Ras-related protein Rab-11A to promote poor prognosis of non-small-cell lung cancer via β1-integrin. In Journal of cellular and molecular medicine, 25, 8821-8835. doi:10.1111/jcmm.16841. https://pubmed.ncbi.nlm.nih.gov/34363324/
3. De Arras, Lesly, Yang, Ivana V, Lackford, Brad, Schwartz, David A, Alper, Scott. 2012. Spatiotemporal inhibition of innate immunity signaling by the Tbc1d23 RAB-GAP. In Journal of immunology (Baltimore, Md. : 1950), 188, 2905-13. doi:10.4049/jimmunol.1102595. https://pubmed.ncbi.nlm.nih.gov/22312129/
4. Marin-Valencia, Isaac, Gerondopoulos, Andreas, Zaki, Maha S, Barr, Francis A, Gleeson, Joseph G. 2017. Homozygous Mutations in TBC1D23 Lead to a Non-degenerative Form of Pontocerebellar Hypoplasia. In American journal of human genetics, 101, 441-450. doi:10.1016/j.ajhg.2017.07.015. https://pubmed.ncbi.nlm.nih.gov/28823706/
5. Ivanova, Ekaterina L, Mau-Them, Frédéric Tran, Riazuddin, Saima, van Bokhoven, Hans, Chelly, Jamel. 2017. Homozygous Truncating Variants in TBC1D23 Cause Pontocerebellar Hypoplasia and Alter Cortical Development. In American journal of human genetics, 101, 428-440. doi:10.1016/j.ajhg.2017.07.010. https://pubmed.ncbi.nlm.nih.gov/28823707/
6. Johnson, Dorothy M, Andrew, Deborah J. 2019. Role of tbc1 in Drosophila embryonic salivary glands. In BMC molecular and cell biology, 20, 19. doi:10.1186/s12860-019-0198-z. https://pubmed.ncbi.nlm.nih.gov/31242864/
7. Navarro Negredo, Paloma, Edgar, James R, Manna, Paul T, Antrobus, Robin, Robinson, Margaret S. 2018. The WDR11 complex facilitates the tethering of AP-1-derived vesicles. In Nature communications, 9, 596. doi:10.1038/s41467-018-02919-4. https://pubmed.ncbi.nlm.nih.gov/29426865/
8. Laugwitz, Lucia, Buchert, Rebecca, Groeschel, Samuel, Krägeloh-Mann, Ingeborg, Haack, Tobias B. 2020. Pontocerebellar hypoplasia type 11: Does the genetic defect determine timing of cerebellar pathology? In European journal of medical genetics, 63, 103938. doi:10.1016/j.ejmg.2020.103938. https://pubmed.ncbi.nlm.nih.gov/32360255/
9. Victorino, Francisco, Alper, Scott. . Identifying novel spatiotemporal regulators of innate immunity. In Immunologic research, 55, 3-9. doi:10.1007/s12026-012-8344-0. https://pubmed.ncbi.nlm.nih.gov/22926826/
10. Cheng, Bi-Hua, Liu, Yunlong, Xuei, Xiaoling, Durant, Pamela J, Lee, Chao-Hung. 2010. Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages. In BMC microbiology, 10, 103. doi:10.1186/1471-2180-10-103. https://pubmed.ncbi.nlm.nih.gov/20377877/