Dlg2-flox 基因敲除小鼠

下单100%中奖,最高可得千元京东卡
复苏/繁育服务
产品名称

Dlg2-flox 基因敲除小鼠

产品编号

S-CKO-08041

品系全称

C57BL/6JCya-Dlg2em1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-23859-Dlg2-B6J-VA

品系状态

使用本品系发表的文献需注明: Dlg2-flox 基因敲除小鼠 mice (Strain S-CKO-08041) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
cKO小鼠库模型
Hippo信号通路

基本信息

基因研究概述

质控标准

基因
基因全称
discs large MAGUK scaffold protein 2
基因别称
A330103J02Rik,B230218P12Rik,B330007M19Rik,Dlgh2,Gm1197,Gm21505,PSD93
染色体号
Chr 7 (Mouse)
转录本 ID
NCBI: NM_011807.3 | Ensembl: ENSMUST00000107196
修饰方式
条件性基因敲除
靶向范围
Exon 6
敲除长度
~670 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:1344351Mice homozygous for a knock-out allele display lower surface expression of NMDA receptor (NMDAR) subunits NR2A and NR2B in dorsal horn neurons and significantly reduced NMDAR-mediated excitatory synaptic currents and NMDAR-dependent persistent inflammatory or nerve injury-induced neuropathic pain.
DLG2,也称为Discs large homolog 2,是一种重要的支架蛋白,属于膜相关鸟苷酸激酶(MAGUK)蛋白超家族。DLG2在细胞膜中与多种蛋白相互作用,包括NMDA受体、钾通道和细胞骨架调节因子,从而调节突触功能、细胞极性和信号传导。DLG2在神经系统中发挥重要作用,其表达和功能的异常与多种神经发育和精神疾病相关,包括精神分裂症、自闭症谱系障碍和智力障碍[2,3,4,7,8]。

DLG2基因位于人类11号染色体上,该基因的缺失或突变与高风险神经母细胞瘤(NB)相关。神经母细胞瘤是一种儿童常见的神经嵴肿瘤,具有高度的遗传异质性。DLG2基因的表达水平与NB患者的预后、肿瘤分期和MYCN状态密切相关。研究发现,DLG2基因表达水平较低与NB患者的不良预后相关[1]。DLG2基因缺失或表达下调导致细胞周期进展失控,促进肿瘤细胞增殖,进而导致NB的发生和发展[1,6]。此外,DLG2基因的表达还受到MYCN基因扩增的影响。MYCN基因扩增是NB中最常见的基因改变之一,其扩增导致DLG2基因表达下调,进一步促进肿瘤细胞的生长和转移[1]。

DLG2基因的表达还与DNA损伤修复和基因组稳定性相关。研究发现,DLG2基因缺失或表达下调导致DNA损伤修复途径的缺陷,使细胞对DNA损伤的敏感性增加,进而导致基因组不稳定和肿瘤的发生[5]。DLG2基因的表达还与突触可塑性和认知功能相关。DLG2基因缺失或表达下调导致突触功能异常,进而影响认知功能,如学习、记忆和社交行为[2,3,4,7,8]。

综上所述,DLG2基因在神经系统中发挥重要作用,其表达和功能的异常与多种神经发育和精神疾病相关。DLG2基因缺失或表达下调导致细胞周期进展失控、DNA损伤修复缺陷和突触功能异常,进而导致肿瘤的发生和发展、基因组不稳定和认知功能障碍。DLG2基因的研究有助于深入理解神经发育和精神疾病的发病机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Keane, Simon, Améen, Sophie, Lindlöf, Angelica, Ejeskär, Katarina. 2020. Low DLG2 gene expression, a link between 11q-deleted and MYCN-amplified neuroblastoma, causes forced cell cycle progression, and predicts poor patient survival. In Cell communication and signaling : CCS, 18, 65. doi:10.1186/s12964-020-00553-6. https://pubmed.ncbi.nlm.nih.gov/32312269/
2. Griesius, Simonas, O'Donnell, Cian, Waldron, Sophie, Robinson, Emma S J, Mellor, Jack R. 2022. Reduced expression of the psychiatric risk gene DLG2 (PSD93) impairs hippocampal synaptic integration and plasticity. In Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 47, 1367-1378. doi:10.1038/s41386-022-01277-6. https://pubmed.ncbi.nlm.nih.gov/35115661/
3. Pass, Rachel, Haan, Niels, Humby, Trevor, Hall, Jeremy, Thomas, Kerrie L. 2022. Selective behavioural impairments in mice heterozygous for the cross disorder psychiatric risk gene DLG2. In Genes, brain, and behavior, 21, e12799. doi:10.1111/gbb.12799. https://pubmed.ncbi.nlm.nih.gov/35118804/
4. Yoo, Taesun, Joshi, Shambhu, Prajapati, Sanjaya, Kim, Eunjoon, Kim, Soo Young. 2022. A Deficiency of the Psychiatric Risk Gene DLG2/PSD-93 Causes Excitatory Synaptic Deficits in the Dorsolateral Striatum. In Frontiers in molecular neuroscience, 15, 938590. doi:10.3389/fnmol.2022.938590. https://pubmed.ncbi.nlm.nih.gov/35966008/
5. Keane, Simon, de Weerd, Hendrik A, Ejeskär, Katarina. 2022. DLG2 impairs dsDNA break repair and maintains genome integrity in neuroblastoma. In DNA repair, 112, 103302. doi:10.1016/j.dnarep.2022.103302. https://pubmed.ncbi.nlm.nih.gov/35217496/
6. Keane, Simon, Martinsson, Tommy, Kogner, Per, Ejeskär, Katarina. 2021. The loss of DLG2 isoform 7/8, but not isoform 2, is critical in advanced staged neuroblastoma. In Cancer cell international, 21, 170. doi:10.1186/s12935-021-01851-w. https://pubmed.ncbi.nlm.nih.gov/33726762/
7. Ruzzo, Elizabeth K, Pérez-Cano, Laura, Jung, Jae-Yoon, Geschwind, Daniel H, Wall, Dennis P. . Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks. In Cell, 178, 850-866.e26. doi:10.1016/j.cell.2019.07.015. https://pubmed.ncbi.nlm.nih.gov/31398340/
8. Yoo, Taesun, Kim, Sun-Gyun, Yang, Soo Hyun, Kim, Eunjoon, Kim, Soo Young. 2020. A DLG2 deficiency in mice leads to reduced sociability and increased repetitive behavior accompanied by aberrant synaptic transmission in the dorsal striatum. In Molecular autism, 11, 19. doi:10.1186/s13229-020-00324-7. https://pubmed.ncbi.nlm.nih.gov/32164788/