Ttll5-KO 基因敲除小鼠

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产品名称

Ttll5-KO 基因敲除小鼠

产品编号

S-KO-16507

品系全称

C57BL/6JCya-Ttll5em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-320244-Ttll5-B6J-VB

品系状态

使用本品系发表的文献需注明: Ttll5-KO 基因敲除小鼠 mice (Strain S-KO-16507) 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
tubulin tyrosine ligase-like family, member 5
基因别称
1700048H13Rik,2310009M18Rik,4930556H18Rik,D630041K24Rik,Stamp,mKIAA0998
染色体号
Chr 12 (Mouse)
转录本 ID
NCBI: NM_001081423 | Ensembl: ENSMUST00000040179
修饰方式
全身性基因敲除
靶向范围
Exon 6
敲除长度
~0.9 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:2443657Mice homozygous for a hypomorphic allele exhibit male infertility associated with abnormal sperm morphology and reduced tubulin polyglutamylation in the spermatozoa.
TTLL5(tubulin tyrosine ligase-like family member 5)基因编码的蛋白质是一种重要的管蛋白谷氨酰化酶,它在细胞内具有多种功能。管蛋白是构成细胞骨架的重要成分,其谷氨酰化修饰对微管的功能和稳定性具有重要作用。TTLL5基因的突变与多种视网膜疾病相关,包括锥形营养不良、锥形-杆形营养不良和黄斑变性等[2,3,4,6,7,8,9]。此外,TTLL5基因的突变还与男性不育相关[4,5]。

在葡萄糖剥夺条件下,TTLL5基因与GFAT1(glutamine-fructose-6-phosphate amidotransferase 1)和TAB1(transforming growth factor β-activated kinase 1 binding protein 1)相互作用,形成TTLL5-GFAT1-TAB1复合物。GFAT1是一种参与HBP(hexosamine biosynthesis pathway)的酶,其代谢活性产生谷氨酸,进一步促进TTLL5介导的TAB1谷氨酰化。TAB1的谷氨酰化增强了p38 MAPK(mitogen-activated protein kinase)的招募和激活,进而促进自噬的发生,保护肿瘤细胞在葡萄糖缺乏条件下的生存[1]。

TTLL5基因的突变导致管蛋白的谷氨酰化水平降低,进而影响微管的功能和稳定性。在视网膜细胞中,TTLL5的突变导致光感受器细胞变性,出现锥形营养不良、锥形-杆形营养不良和黄斑变性等疾病[2,3,6,7,8,9]。此外,TTLL5基因的突变还导致精子形态异常和运动能力下降,进而影响男性生育能力[4,5]。

TTLL5基因的突变与多种视网膜疾病相关,包括锥形营养不良、锥形-杆形营养不良和黄斑变性等。TTLL5基因的突变导致管蛋白的谷氨酰化水平降低,进而影响微管的功能和稳定性。此外,TTLL5基因的突变还导致精子形态异常和运动能力下降,进而影响男性生育能力。这些研究结果表明,TTLL5基因在细胞骨架的稳定性和功能、视网膜发育和男性生育能力中发挥着重要作用。

参考文献:
1. Wei, Shupei, Zhao, Qin, Zheng, Ke, Chen, Tao, Zhong, Nanshan. 2022. GFAT1-linked TAB1 glutamylation sustains p38 MAPK activation and promotes lung cancer cell survival under glucose starvation. In Cell discovery, 8, 77. doi:10.1038/s41421-022-00423-0. https://pubmed.ncbi.nlm.nih.gov/35945223/
2. Smirnov, Vasily, Grunewald, Olivier, Muller, Jean, Boulanger-Scemama, Elise, Dhaenens, Claire-Marie. 2021. Novel TTLL5 Variants Associated with Cone-Rod Dystrophy and Early-Onset Severe Retinal Dystrophy. In International journal of molecular sciences, 22, . doi:10.3390/ijms22126410. https://pubmed.ncbi.nlm.nih.gov/34203883/
3. Del Pozo-Valero, Marta, Riveiro-Alvarez, Rosa, Martin-Merida, Inmaculada, Avila-Fernandez, Almudena, Ayuso, Carmen. . Impact of Next Generation Sequencing in Unraveling the Genetics of 1036 Spanish Families With Inherited Macular Dystrophies. In Investigative ophthalmology & visual science, 63, 11. doi:10.1167/iovs.63.2.11. https://pubmed.ncbi.nlm.nih.gov/35119454/
4. Bedoni, Nicola, Haer-Wigman, Lonneke, Vaclavik, Veronika, Munier, Francis L, Rivolta, Carlo. . Mutations in the polyglutamylase gene TTLL5, expressed in photoreceptor cells and spermatozoa, are associated with cone-rod degeneration and reduced male fertility. In Human molecular genetics, 25, 4546-4555. doi:10.1093/hmg/ddw282. https://pubmed.ncbi.nlm.nih.gov/28173158/
5. Lee, Geun-Shik, He, Yuanzheng, Dougherty, Edward J, Dean, Jurrien, Simons, S Stoney. 2013. Disruption of Ttll5/stamp gene (tubulin tyrosine ligase-like protein 5/SRC-1 and TIF2-associated modulatory protein gene) in male mice causes sperm malformation and infertility. In The Journal of biological chemistry, 288, 15167-80. doi:10.1074/jbc.M113.453936. https://pubmed.ncbi.nlm.nih.gov/23558686/
6. Sergouniotis, Panagiotis I, Chakarova, Christina, Murphy, Cian, Webster, Andrew R, Plagnol, Vincent. . Biallelic variants in TTLL5, encoding a tubulin glutamylase, cause retinal dystrophy. In American journal of human genetics, 94, 760-9. doi:10.1016/j.ajhg.2014.04.003. https://pubmed.ncbi.nlm.nih.gov/24791901/
7. Kolawole, Olubayo U, Gregory-Evans, Cheryl Y, Bikoo, Riyaz, Huang, Albert Z, Gregory-Evans, Kevin. 2023. Novel pathogenic variants in Tubulin Tyrosine Like 5 (TTLL5) associated with cone-dominant retinal dystrophies and an abnormal optical coherence tomography phenotype. In Molecular vision, 29, 329-337. doi:. https://pubmed.ncbi.nlm.nih.gov/38264610/
8. Kazmierczak de Camargo, João Paulo, Prezia, Giovanna Nazaré de Barros, Shiokawa, Naoye, Rosati, Roberto, Beate Winter Boldt, Angelica. 2022. New Insights on the Regulatory Gene Network Disturbed in Central Areolar Choroidal Dystrophy-Beyond Classical Gene Candidates. In Frontiers in genetics, 13, 886461. doi:10.3389/fgene.2022.886461. https://pubmed.ncbi.nlm.nih.gov/35656327/
9. Sun, Xun, Park, James H, Gumerson, Jessica, Roll-Mecak, Antonina, Li, Tiansen. 2016. Loss of RPGR glutamylation underlies the pathogenic mechanism of retinal dystrophy caused by TTLL5 mutations. In Proceedings of the National Academy of Sciences of the United States of America, 113, E2925-34. doi:10.1073/pnas.1523201113. https://pubmed.ncbi.nlm.nih.gov/27162334/