Afdn-flox 基因敲除小鼠

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产品名称

Afdn-flox 基因敲除小鼠

产品编号

S-CKO-03744

品系全称

C57BL/6JCya-Afdnem1flox/Cya

品系背景

C57BL/6JCya

品系编号

CKOCMP-17356-Afdn-B6J-VA

品系状态

使用本品系发表的文献需注明: Afdn-flox 基因敲除小鼠 mice (Strain S-CKO-03744) 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
afadin, adherens junction formation factor
基因别称
5033403D15Rik,AF6,Af-6,Afadin,Gm314,I-afadin,Mllt4,S-afadin
染色体号
Chr 17 (Mouse)
转录本 ID
NCBI: NM_010806.1 | Ensembl: ENSMUST00000139666
修饰方式
条件性基因敲除
靶向范围
Exon 3
敲除长度
~613 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:1314653Homozygous null mice display embryonic lethality, abnormal ectoderm development including disrupted cell junctions, and absence of the somites, notochord, allantois, and neural folds.
AFDN,也称为AF6,是一种细胞粘附分子(CAMs),编码AFADIN,一种重要的CAM,形成钙非依赖性复合物与nectins 1和4(由基因PVRL1和PVRL4编码)结合。AFDN在多种生物学过程中发挥作用,包括细胞粘附、迁移和信号传导。此外,AFDN还参与肿瘤的发生和发展,其表达和功能异常与多种癌症的发生和发展密切相关。

研究表明,AFDN基因的突变与非综合征性唇裂伴或不伴腭裂(nsCL±P)的发生风险相关[7]。这些突变包括p.Met1164Ile、p.Thr453Asn、p.Pro1638Ala、p.Arg669Gln、p.Ala1717Val和p.Arg1596His,以及一个新型剪接p.Leu1588Leu突变。计算分析表明,这些氨基酸改变影响AFDN与其他裂隙相关基因,包括nectins(PVRL1、PVRL2、PVRL3和PVRL4)、CDH1、CTNNA1和CTNND1的相互作用。

此外,AFDN的表达和功能异常与急性髓系白血病(AML)的发生和发展密切相关。研究表明,KMT2A/AFDN基因融合是AML的一种重要遗传改变,与不良预后相关[1,2,4,8]。KMT2A/AFDN基因融合的发生机制包括5'KMT2A插入事件[1]和同源有丝分裂重组(HMR)[3]。此外,AFDN基因的表达还受到DNA甲基化等表观遗传调控的影响[5,6]。

综上所述,AFDN是一种重要的细胞粘附分子,参与细胞粘附、迁移和信号传导等生物学过程。AFDN基因的突变和表达异常与nsCL±P和AML等多种疾病的发生和发展密切相关。AFDN的研究有助于深入理解细胞粘附分子在疾病发生和发展中的作用机制,为疾病的治疗和预防提供新的思路和策略。

参考文献:
1. Berg, Holly E, Greipp, Patricia T, Baughn, Linda B, Jackson, Courtney C, Peterson, Jess F. . Detection of a Cryptic KMT2A/AFDN Gene Fusion [ins(6;11)(q27;q23q23)] in a Pediatric Patient with Newly Diagnosed Acute Myeloid Leukemia. In Laboratory medicine, 53, e95-e99. doi:10.1093/labmed/lmab109. https://pubmed.ncbi.nlm.nih.gov/34894139/
2. Bill, Marius, Mrózek, Krzysztof, Kohlschmidt, Jessica, Byrd, John C, Bloomfield, Clara D. 2020. Mutational landscape and clinical outcome of patients with de novo acute myeloid leukemia and rearrangements involving 11q23/KMT2A. In Proceedings of the National Academy of Sciences of the United States of America, 117, 26340-26346. doi:10.1073/pnas.2014732117. https://pubmed.ncbi.nlm.nih.gov/33020282/
3. Papenhausen, Peter, Kelly, Carla A, Zhang, Zhenxi, Penton, Andrea. 2023. Mitotic recombinatory evolution in acute leukemia. In Cancer genetics, 274-275, 33-40. doi:10.1016/j.cancergen.2023.02.003. https://pubmed.ncbi.nlm.nih.gov/36966725/
4. van Weelderen, Romy E, Harrison, Christine J, Klein, Kim, Zwaan, C Michel, Kaspers, Gertjan J L. . Optimized cytogenetic risk-group stratification of KMT2A-rearranged pediatric acute myeloid leukemia. In Blood advances, 8, 3200-3213. doi:10.1182/bloodadvances.2023011771. https://pubmed.ncbi.nlm.nih.gov/38621200/
5. Lai, Yuexing, Xu, Ping, Wang, Jing, Wang, Lin, Meng, Yuchen. 2020. Tumour suppressive long non-coding RNA AFDN-DT inhibits gastric cancer invasion via transcriptional regulation. In Journal of cellular and molecular medicine, 24, 3157-3166. doi:10.1111/jcmm.14988. https://pubmed.ncbi.nlm.nih.gov/31981317/
6. Xiang, Xiao, Yu, Du, Li, Zhuangzhuang, Pijlman, Gorben P, Qiu, Yafeng. 2024. Japanese encephalitis virus-induced DNA methylation contributes to blood-brain barrier permeability by modulating tight junction protein expression. In Journal of neuroinflammation, 21, 277. doi:10.1186/s12974-024-03266-6. https://pubmed.ncbi.nlm.nih.gov/39468601/
7. Awotoye, Waheed, Mossey, Peter A, Hetmanski, Jacqueline B, Murray, Jeffrey C, Butali, Azeez. 2022. Damaging Mutations in AFDN Contribute to Risk of Nonsyndromic Cleft Lip With or Without Cleft Palate. In The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association, 61, 697-705. doi:10.1177/10556656221135926. https://pubmed.ncbi.nlm.nih.gov/36384317/
8. Xu, Yi, Li, Shengwen Calvin, Xiao, Jeffrey, Cao, Huynh, Zhong, Jiang F. 2025. Exploring treatment-driven subclonal evolution of prognostic triple biomarkers: Dual gene fusions and chimeric RNA variants in novel subtypes of acute myeloid leukemia patients with KMT2A rearrangement. In Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy, 79, 101199. doi:10.1016/j.drup.2024.101199. https://pubmed.ncbi.nlm.nih.gov/39823827/