Dlg2-KO 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-KO 基因敲除小鼠

产品编号

S-KO-06989

品系全称

C57BL/6JCya-Dlg2em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-23859-Dlg2-B6J-VA

品系状态

使用本品系发表的文献需注明: Dlg2-KO 基因敲除小鼠 mice (Strain S-KO-06989) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
KO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
全身性基因敲除
靶向范围
Exon 5
敲除长度
~125 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(Discs large homolog 2)是一种重要的细胞骨架蛋白,属于膜相关鸟苷酸激酶(MAGUK)蛋白超家族。MAGUK蛋白在细胞信号传导、细胞粘附和细胞极性中发挥重要作用。DLG2蛋白在神经元中特别丰富,尤其是在突触后密度(PSD)区域,与NMDA受体、钾通道和细胞骨架调节因子相互作用。DLG2的这些相互作用对于突触可塑性、学习和记忆至关重要。DLG2基因的变异与多种神经发育和精神疾病有关,包括精神分裂症、自闭症谱系障碍(ASD)和智力障碍。

DLG2基因在神经母细胞瘤(NB)的发生和发展中也起着重要作用。DLG2基因位于11号染色体上,该染色体在NB患者中经常发生缺失。DLG2基因表达水平的降低与NB患者的预后不良、肿瘤分期和MYCN基因扩增状态相关。DLG2基因表达水平的降低会导致细胞周期加速,增加细胞在G2/M期的比例,并减少细胞在G1期的比例。此外,DLG2基因表达水平的降低还会导致DNA损伤修复缺陷,从而影响基因组完整性。DLG2基因表达水平的降低可能是由于MYCN基因扩增或11q染色体缺失所致。

DLG2基因有多个不同的亚型,其中含有L27结构域的DLG2亚型在神经母细胞瘤的发生和发展中起着关键作用。DLG2-isoform 7/8是含有L27结构域的DLG2亚型,在神经母细胞瘤中表达下调。DLG2-isoform 7/8与LIN7A蛋白结合,调节细胞极性和信号传导,从而影响肿瘤细胞增殖和存活。DLG2-isoform 7/8表达水平的降低会导致LIN7A蛋白表达下调,从而增加肿瘤细胞增殖和存活。

综上所述,DLG2基因在神经发育和精神疾病以及神经母细胞瘤的发生和发展中发挥着重要作用。DLG2基因表达水平的降低与多种疾病的发生和发展相关,包括神经母细胞瘤、精神分裂症、自闭症谱系障碍和智力障碍。DLG2基因的研究有助于深入理解这些疾病的发病机制,为疾病的治疗和预防提供新的思路和策略[1,2,3,4,5,6,7,8,9,10]。

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. 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/
4. 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/
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. Bertini, Veronica, Milone, Roberta, Cristofani, Paola, Valetto, Angelo, Battini, Roberta. 2022. Enhancing DLG2 Implications in Neuropsychiatric Disorders: Analysis of a Cohort of Eight Patients with 11q14.1 Imbalances. In Genes, 13, . doi:10.3390/genes13050859. https://pubmed.ncbi.nlm.nih.gov/35627244/
8. Lin, Hongchun, Ma, Xinxin, Sun, Yuxiang, Thomas, Sandhya Sara, Hu, Zhaoyong. 2022. Decoding the transcriptome of denervated muscle at single-nucleus resolution. In Journal of cachexia, sarcopenia and muscle, 13, 2102-2117. doi:10.1002/jcsm.13023. https://pubmed.ncbi.nlm.nih.gov/35726356/
9. 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/
10. Turan, Ihsan, Demir, Korcan, Mengen, Eda, Yüksel, Bilgin, Topaloglu, Ali Kemal. 2021. DLG2 Mutations in the Etiology of Pubertal Delay and Idiopathic Hypogonadotropic Hypogonadism. In Hormone research in paediatrics, 94, 364-368. doi:10.1159/000520409. https://pubmed.ncbi.nlm.nih.gov/34695822/