Fezf2-flox 基因敲除小鼠

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产品名称

Fezf2-flox 基因敲除小鼠

产品编号

S-CKO-11873

品系全称

C57BL/6JCya-Fezf2em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-54713-Fezf2-B6J-VA

品系状态

使用本品系发表的文献需注明: Fezf2-flox 基因敲除小鼠 mice (Strain S-CKO-11873) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO小鼠库模型

基本信息

基因研究概述

质控标准

基因
基因全称
Fez family zinc finger 2
基因别称
Fez,Fezl,Zfp312
染色体号
Chr 14 (Mouse)
转录本 ID
NCBI: NM_080433 | Ensembl: ENSMUST00000022262
修饰方式
条件性基因敲除
靶向范围
Exon 2~5
敲除长度
~3.9 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:1859823Homozygotes for a null allele show hyperactivity, altered feeding behavior leading to delayed growth and premature death, and impaired formation of subplate neurons and thalamocortical projections. Homozygotes for another allele lack a corpus callosum and show severe subcortical projection defects.
Fezf2,也称为Fez family zinc finger 2,是一种重要的转录因子,对神经发育起着关键作用。Fezf2通过调控基因表达,影响神经元分化和神经网络的形成。Fezf2在多种神经元亚型中表达,包括皮层的L5-6_Fezf2和L2-3_Cux2神经元,以及GABAergic interneurons中的Sst和Pvalb神经元[1]。此外,Fezf2还在小鼠的皮层脊髓运动神经元(CSMN)中表达,并直接诱导CSMN的谷氨酸能身份,抑制其GABA能命运[2]。

Fezf2在免疫系统中也发挥着重要作用。Fezf2在胸腺髓质上皮细胞中特异性表达,调节大量组织限制性抗原的表达,并抑制自身免疫反应的发生[3]。Fezf2还在胸腺Tuft细胞(Tuft mTECs)的发育中发挥调控作用,影响胸腺的自身免疫耐受功能[6]。此外,Fezf2还参与了胸腺髓质上皮细胞的发育,并调节其自我肽库的表达[6]。

Fezf2的突变与神经发育障碍有关。罕见的Fezf2基因突变可能导致神经发育障碍,包括发育迟缓、智力障碍、自闭症和/或注意力缺陷/多动障碍[4]。Fezf2的突变会影响神经元命运的抉择,导致神经元发育异常和细胞死亡[5]。

Fezf2还与肿瘤发生有关。在鼻咽癌中,Fezf2的表达常常被甲基化沉默,导致肿瘤抑制基因EZH2和MDM2的表达上调,从而促进肿瘤的发生和发展[7]。Fezf2通过直接结合到EZH2和MDM2的启动子上,抑制其表达,发挥肿瘤抑制因子的作用[7]。

综上所述,Fezf2是一种重要的转录因子,参与调控神经发育、免疫系统和肿瘤发生。Fezf2在神经元亚型特异性基因表达、神经网络形成、自身免疫耐受和肿瘤抑制等方面发挥着关键作用。深入研究Fezf2的生物学功能和调控机制,有助于理解神经系统疾病、自身免疫疾病和肿瘤的发生机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Pfisterer, Ulrich, Petukhov, Viktor, Demharter, Samuel, Kharchenko, Peter V, Khodosevich, Konstantin. 2020. Identification of epilepsy-associated neuronal subtypes and gene expression underlying epileptogenesis. In Nature communications, 11, 5038. doi:10.1038/s41467-020-18752-7. https://pubmed.ncbi.nlm.nih.gov/33028830/
2. Lodato, Simona, Molyneaux, Bradley J, Zuccaro, Emanuela, Gifford, David K, Arlotta, Paola. 2014. Gene co-regulation by Fezf2 selects neurotransmitter identity and connectivity of corticospinal neurons. In Nature neuroscience, 17, 1046-54. doi:10.1038/nn.3757. https://pubmed.ncbi.nlm.nih.gov/24997765/
3. Takaba, Hiroyuki, Takayanagi, Hiroshi. 2017. The Mechanisms of T Cell Selection in the Thymus. In Trends in immunology, 38, 805-816. doi:10.1016/j.it.2017.07.010. https://pubmed.ncbi.nlm.nih.gov/28830733/
4. Garber, Alison, Weingarten, Lisa S, Abreu, Nicolas J, Steigerwald, Connolly, Chung, Wendy K. 2024. Rare predicted deleterious FEZF2 variants are associated with a neurodevelopmental phenotype. In American journal of medical genetics. Part A, 194, e63578. doi:10.1002/ajmg.a.63578. https://pubmed.ncbi.nlm.nih.gov/38425142/
5. Hirata-Fukae, Chiho, Hirata, Tsutomu. 2014. The zinc finger gene Fezf2 is required for the development of excitatory neurons in the basolateral complex of the amygdala. In Developmental dynamics : an official publication of the American Association of Anatomists, 243, 1030-6. doi:10.1002/dvdy.24137. https://pubmed.ncbi.nlm.nih.gov/24723342/
6. Lammers, Sören, Barrera, Victor, Brennecke, Philip, von Andrian, Ulrich H, Rattay, Kristin. 2024. Ehf and Fezf2 regulate late medullary thymic epithelial cell and thymic tuft cell development. In Frontiers in immunology, 14, 1277365. doi:10.3389/fimmu.2023.1277365. https://pubmed.ncbi.nlm.nih.gov/38420512/
7. Shu, Xing-Sheng, Li, Lili, Ji, Mingfang, Chan, Anthony T C, Tao, Qian. 2013. FEZF2, a novel 3p14 tumor suppressor gene, represses oncogene EZH2 and MDM2 expression and is frequently methylated in nasopharyngeal carcinoma. In Carcinogenesis, 34, 1984-93. doi:10.1093/carcin/bgt165. https://pubmed.ncbi.nlm.nih.gov/23677067/