Wdr45b-KO 基因敲除小鼠

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产品名称

Wdr45b-KO 基因敲除小鼠

产品编号

S-KO-11945

品系全称

C57BL/6JCya-Wdr45bem1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-66840-Wdr45b-B6J-VA

品系状态

使用本品系发表的文献需注明: Wdr45b-KO 基因敲除小鼠 mice (Strain S-KO-11945) 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
WD repeat domain 45B
基因别称
0610008N23Rik,D16Bwg0193e,WIPI-3,Wdr45l
染色体号
Chr 11 (Mouse)
转录本 ID
NCBI: NM_025793.3 | Ensembl: ENSMUST00000026173
修饰方式
全身性基因敲除
靶向范围
Exon 3~6
敲除长度
~5832 bp
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:1914090Conditional homozygous knockout in neurons affects the Golgi apparatus and mitochondria, which impairs alternative autophagy and leads to neuronal degeneration in the brain and motor deficits.
Wdr45b,也称为WIPI3(WD-repeat protein Interacting with PhosphoInositides 3),是一种重要的自噬相关基因。自噬是一种细胞内的质量控制机制,通过降解折叠错误的蛋白质和受损的细胞器,在维持细胞稳态中发挥关键作用。Wdr45b作为自噬相关的磷脂酰肌醇-3-磷酸(PtdIns3P)效应蛋白,在自噬体的形成过程中发挥重要作用。在哺乳动物细胞中,Wdr45b属于Atg18蛋白家族,该家族还包括WIPI1、WIPI2和WIPI4。Wdr45b的突变与多种人类疾病相关,包括智力障碍、神经退行性疾病和肿瘤等[1]。

研究发现,Wdr45b在自噬过程中发挥重要作用。Wdr45b的缺失会导致自噬体形成障碍,影响自噬的进行。此外,Wdr45b的突变还与β-螺旋桨蛋白相关的神经退行性疾病(BPAN)有关。BPAN是一种罕见的神经退行性疾病,患者表现为大脑铁积累、智力障碍、运动障碍和癫痫等症状。研究表明,WDR45B基因突变会导致WIPI4蛋白功能异常,从而影响自噬过程,导致神经细胞功能障碍和死亡[2]。

除了在自噬过程中的作用,Wdr45b还与肿瘤的发生和发展密切相关。研究发现,Wdr45b在肝细胞癌(HCC)中高表达,并通过Akt/mTOR信号通路促进肿瘤细胞的增殖和迁移[3]。此外,Wdr45b还与肿瘤相关巨噬细胞(TAMs)的极化相关,研究发现,WDR45B+ TAMs在肝转移瘤中富集,并表现出M2型极化,与患者的不良预后相关[4]。

综上所述,Wdr45b作为一种重要的自噬相关基因,在维持细胞稳态和肿瘤发生发展中发挥重要作用。Wdr45b的突变与多种人类疾病相关,包括智力障碍、神经退行性疾病和肿瘤等。深入研究Wdr45b的功能和机制,有助于揭示相关疾病的发病机制,为疾病的治疗和预防提供新的思路和策略[5][6][7][8][9][10]。

参考文献:
1. Gui, Menghui, Huang, Shilin, Li, Shizhou, Cao, Pengbo, Zhou, Gangqiao. 2024. Integrative single-cell transcriptomic analyses reveal the cellular ontological and functional heterogeneities of primary and metastatic liver tumors. In Journal of translational medicine, 22, 206. doi:10.1186/s12967-024-04947-9. https://pubmed.ncbi.nlm.nih.gov/38414027/
2. Almannai, Mohammed, Marafi, Dana, El-Hattab, Ayman W. 2022. WIPI proteins: Biological functions and related syndromes. In Frontiers in molecular neuroscience, 15, 1011918. doi:10.3389/fnmol.2022.1011918. https://pubmed.ncbi.nlm.nih.gov/36157071/
3. Li, Jiahao, Chen, Lansi, Pang, Jingjing, Xiao, Shu-Yuan, Li, Yueying. 2023. Autophagy-Related Gene WD Repeat Domain 45B Promotes Tumor Proliferation and Migration of Hepatocellular Carcinoma through the Akt/mTOR Signaling Pathway. In Diagnostics (Basel, Switzerland), 13, . doi:10.3390/diagnostics13050906. https://pubmed.ncbi.nlm.nih.gov/36900050/
4. Zhang, Jinhong, Lu, Yan, Tian, Xiaoyu, Yang, Zuozhen, Wang, Xiuxia. 2022. A homozygous variant of WDR45B results in global developmental delay: Additional case and literature review. In Molecular genetics & genomic medicine, 10, e2036. doi:10.1002/mgg3.2036. https://pubmed.ncbi.nlm.nih.gov/35962600/
5. Ji, Cuicui, Zhao, Hongyu, Li, Dongfang, Zhang, Hong, Zhao, Yan G. 2019. Role of Wdr45b in maintaining neural autophagy and cognitive function. In Autophagy, 16, 615-625. doi:10.1080/15548627.2019.1632621. https://pubmed.ncbi.nlm.nih.gov/31238825/
6. Suleiman, J, Allingham-Hawkins, D, Hashem, M, Alkuraya, F S, El-Hattab, A W. 2017. WDR45B-related intellectual disability, spastic quadriplegia, epilepsy, and cerebral hypoplasia: A consistent neurodevelopmental syndrome. In Clinical genetics, 93, 360-364. doi:10.1111/cge.13054. https://pubmed.ncbi.nlm.nih.gov/28503735/
7. Proikas-Cezanne, Tassula, Haas, Maximilian L, Pastor-Maldonado, Carmen J, Schüssele, David S. 2023. Human WIPI β-propeller function in autophagy and neurodegeneration. In FEBS letters, 598, 127-139. doi:10.1002/1873-3468.14782. https://pubmed.ncbi.nlm.nih.gov/38058212/
8. Xun, Qiufen, Kuang, Jiulong, Yang, Qing, Wang, Wei, Zhu, Guofeng. 2021. GLCCI1 reduces collagen deposition and airway hyper-responsiveness in a mouse asthma model through binding with WD repeat domain 45B. In Journal of cellular and molecular medicine, 25, 6573-6583. doi:10.1111/jcmm.16658. https://pubmed.ncbi.nlm.nih.gov/34050597/
9. Younis, N S, Mohamed, M E, Alolayan, A A, AlOmran, Z A, Almostafa, M M. . Identification of epilepsy concomitant candidate genes recognized in Saudi epileptic patients. In European review for medical and pharmacological sciences, 26, 2143-2157. doi:10.26355/eurrev_202203_28362. https://pubmed.ncbi.nlm.nih.gov/35363364/
10. Shimizu, Takahiro, Tamura, Norito, Nishimura, Taki, Yamamoto, Hayashi, Mizushima, Noboru. . Comprehensive analysis of autophagic functions of WIPI family proteins and their implications for the pathogenesis of β-propeller associated neurodegeneration. In Human molecular genetics, 32, 2623-2637. doi:10.1093/hmg/ddad096. https://pubmed.ncbi.nlm.nih.gov/37364041/