Ap1s2-KO 基因敲除小鼠

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产品名称

Ap1s2-KO 基因敲除小鼠

产品编号

S-KO-00559

品系全称

C57BL/6JCya-Ap1s2em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-108012-Ap1s2-B6J-VA

品系状态

使用本品系发表的文献需注明: Ap1s2-KO 基因敲除小鼠 mice (Strain S-KO-00559) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
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小计:
询价

基本信息

基因研究概述

质控标准

基因
基因全称
adaptor-related protein complex 1, sigma 2 subunit
基因别称
1500012A13Rik,EST1
染色体号
Chr X (Mouse)
转录本 ID
NCBI: NM_026887.3 | Ensembl: ENSMUST00000112294
修饰方式
全身性基因敲除
靶向范围
Exon 2
敲除长度
~179 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:1889383Targeted inactivation of the sigma1B isoform results in impaired synaptic vesicle recycling, hypoactivity, impaired balance, deficits in long-term spatial memory, lipodystrophy, and abnormal adipocyte differentiation.
AP1S2,也称为适配蛋白1复合体σ2亚基,是适配蛋白1复合体(AP-1)的一个亚基。AP-1复合体是一个由四个亚基组成的异源四聚体,包括两个大亚基(α和β)、一个小亚基(μ)和一个σ亚基(σ1A、σ1B或σ1C)。AP-1复合体在细胞内蛋白运输中发挥着重要作用,通过介导货物蛋白与网格蛋白包被的运输囊泡的结合,参与内吞作用、分泌和膜融合等过程。AP1S2的突变或缺失可能导致细胞内蛋白运输异常,进而影响细胞功能。

AP1S2基因的突变与多种疾病相关,包括炎症性肠病(IBD)、甲状腺癌和神经发育障碍。在IBD中,AP1S2基因的缺失导致巨噬细胞成熟受阻,加剧肠道炎症。研究发现,AP1S2基因缺失的小鼠在DSS诱导的结肠炎模型中表现出更严重的炎症症状,包括巨噬细胞迁移能力增强和M1型巨噬细胞极化增加,但巨噬细胞成熟程度降低[1]。在甲状腺癌中,miR-204-5p下调导致AP1S2表达增加,促进甲状腺癌细胞增殖、迁移和侵袭。miR-204-5p通过抑制AP1S2表达来发挥抑癌作用[2]。

此外,AP1S2基因的突变还与神经发育障碍相关。Pettigrew综合征(PGS)是一种罕见的X连锁智力障碍,由AP1S2基因突变引起。PGS患者的临床表现包括智力障碍、步态延迟、言语障碍、肌张力减退、脑部异常和行为异常等。研究发现,AP1S2基因突变导致蛋白质功能缺失,影响细胞内蛋白运输,进而导致神经发育障碍[3,4,5,6,7,8,9]。

综上所述,AP1S2基因在细胞内蛋白运输和神经发育中发挥着重要作用。AP1S2基因的突变或缺失可能导致多种疾病的发生,包括炎症性肠病、甲状腺癌和神经发育障碍。研究AP1S2基因的功能和突变机制有助于深入理解这些疾病的发病机制,为疾病的诊断、治疗和预防提供新的思路和策略。

参考文献:
1. Lu, Huiying, Zhang, Cui, Wu, Wei, Kolattukudy, Pappachan E, Liu, Zhanju. 2022. MCPIP1 restrains mucosal inflammation by orchestrating the intestinal monocyte to macrophage maturation via an ATF3-AP1S2 axis. In Gut, 72, 882-895. doi:10.1136/gutjnl-2022-327183. https://pubmed.ncbi.nlm.nih.gov/37015751/
2. Gu, Yulu, Zhang, Xin, Li, Yong, Cheng, Yi, Liu, Yawen. 2023. MiR-204-5p-targeted AP1S2 is necessary for papillary thyroid carcinoma. In Molecular and cellular endocrinology, 574, 111993. doi:10.1016/j.mce.2023.111993. https://pubmed.ncbi.nlm.nih.gov/37328093/
3. Huo, Liang, Teng, Ziteng, Wang, Hua, Liu, Xueyan. 2019. A novel splice site mutation in AP1S2 gene for X-linked mental retardation in a Chinese pedigree and literature review. In Brain and behavior, 9, e01221. doi:10.1002/brb3.1221. https://pubmed.ncbi.nlm.nih.gov/30714330/
4. Cappuccio, Gerarda, Torella, Annalaura, Mastrangelo, Mario, Brunetti-Pierri, Nicola, Leuzzi, Vincenzo. 2018. AP1S2-truncating variant in a patient with severe neurodevelopmental disorder and cerebral folate deficiency. In Acta paediatrica (Oslo, Norway : 1992), 108, 564-565. doi:10.1111/apa.14633. https://pubmed.ncbi.nlm.nih.gov/30383884/
5. Zhu, Dengna, Wang, Mingmei, Xu, Yiran, Yang, Fan, Yang, Zuozhen. 2022. Identification of a 5 bp duplicate in the AP1S2 gene of an individual with X-linked intellectual disability. In Neurogenetics, 23, 179-185. doi:10.1007/s10048-022-00691-8. https://pubmed.ncbi.nlm.nih.gov/35391588/
6. Cacciagli, Pierre, Desvignes, Jean-Pierre, Girard, Nadine, Dobyns, William B, Villard, Laurent. 2013. AP1S2 is mutated in X-linked Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome). In European journal of human genetics : EJHG, 22, 363-8. doi:10.1038/ejhg.2013.135. https://pubmed.ncbi.nlm.nih.gov/23756445/
7. Noojarern, Saisuda, Tim-Aroon, Thipwimol, Anurat, Kingthong, Khongkraparn, Arthaporn, Wattanasirichaigoon, Duangrurdee. 2024. A novel AP1S2 variant causing leaky splicing in X-linked intellectual disability: Further delineation and intrafamilial variability. In American journal of medical genetics. Part A, 194, e63639. doi:10.1002/ajmg.a.63639. https://pubmed.ncbi.nlm.nih.gov/38682877/
8. Ballarati, Lucia, Cereda, Anna, Caselli, Rossella, Larizza, Lidia, Giardino, Daniela. 2011. Deletion of the AP1S2 gene in a child with psychomotor delay and hypotonia. In European journal of medical genetics, 55, 124-7. doi:10.1016/j.ejmg.2011.12.001. https://pubmed.ncbi.nlm.nih.gov/22210230/
9. Borck, Guntram, Mollà-Herman, Anahi, Boddaert, Nathalie, Munnich, Arnold, Colleaux, Laurence. . Clinical, cellular, and neuropathological consequences of AP1S2 mutations: further delineation of a recognizable X-linked mental retardation syndrome. In Human mutation, 29, 966-74. doi:10.1002/humu.20531. https://pubmed.ncbi.nlm.nih.gov/18428203/