Adamts10-KO 基因敲除小鼠

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产品名称

Adamts10-KO 基因敲除小鼠

产品编号

S-KO-18695

品系全称

C57BL/6JCya-Adamts10em1/Cya

品系背景

C57BL/6JCya

品系编号

KOCMP-224697-Adamts10-B6J-VB

品系状态

使用本品系发表的文献需注明: Adamts10-KO 基因敲除小鼠 mice (Strain S-KO-18695) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量

基本信息

基因研究概述

质控标准

基因
基因全称
ADAM metallopeptidase with thrombospondin type 1 motif 10
基因别称
9430006O18,Adam-ts10,Adamts-10,Znmp
染色体号
Chr 17 (Mouse)
转录本 ID
NCBI: NM_172619 | Ensembl: ENSMUST00000087623
修饰方式
全身性基因敲除
靶向范围
Exon 2~5
敲除长度
~4.3 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:2449112Mice homozygous for a truncation mutation exhibit decreased body weight and length, shorter long bones, thick skin, altered bone development, abnormalities in the ciliary apparatus of the eye, and increased skeletal muscle mass with increased numbers of smaller skeletal muscle fibers.
Adamts10,也称为A disintegrin and metalloproteinase with thrombospondin motifs 10,是一种属于ADAMTS家族的分泌型蛋白质。ADAMTS家族是由26个分泌型分子组成的大家族,包括两个相关但不同的家族。ADAMTS蛋白酶是锌金属内肽酶,其大部分底物是细胞外基质(ECM)成分,而ADAMTS样蛋白缺乏金属蛋白酶结构域,存在于ECM中,并具有调节ECM组装和/或ADAMTS活性的作用[1]。

Adamts10在人类遗传性疾病中发挥着重要作用。例如,Adamts10基因的突变与Weill-Marchesani综合征(WMS)相关,这是一种罕见的结缔组织疾病,表现为短身材、短指(趾)、关节僵硬和晶状体异位等症状[3][5][6]。Adamts10的突变还会导致原发性开角型青光眼(POAG),这是全球导致失明的主要原因之一[7][8]。Adamts10的突变还会导致晶状体异位和短指(趾)等眼部和骨骼异常[7][8]。

除了遗传性疾病,Adamts10还与多种获得性疾病相关。例如,Adamts10在胃腺癌中表达下调,低表达的患者总体生存率较差。Adamts10过表达可以改变细胞周期,促进凋亡,抑制增殖、迁移和侵袭,并抑制巨噬细胞M2极化,从而创造抗肿瘤微环境[2]。此外,Adamts10在肾透明细胞癌中过表达,其表达与肿瘤分级相关,过表达的患者预后和生存率较低[4]。Adamts10的过表达可以抑制癌细胞增殖、侵袭和迁移,并通过NF-κB信号通路发挥作用[4]。

综上所述,Adamts10是一种重要的ADAMTS家族成员,参与调控细胞外基质的组装和功能,并与多种人类遗传性疾病和获得性疾病相关。Adamts10在WMS、POAG、胃腺癌和肾透明细胞癌等疾病中发挥着重要作用,可能是这些疾病的诊断、预后和治疗的重要靶点。

参考文献:
1. Mead, Timothy J, Apte, Suneel S. 2018. ADAMTS proteins in human disorders. In Matrix biology : journal of the International Society for Matrix Biology, 71-72, 225-239. doi:10.1016/j.matbio.2018.06.002. https://pubmed.ncbi.nlm.nih.gov/29885460/
2. Zhou, Junyi, Li, Tuoyang, Chen, Hao, Huang, Zhenze, Yang, Zuli. 2022. ADAMTS10 inhibits aggressiveness via JAK/STAT/c-MYC pathway and reprograms macrophage to create an anti-malignant microenvironment in gastric cancer. In Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 25, 1002-1016. doi:10.1007/s10120-022-01319-4. https://pubmed.ncbi.nlm.nih.gov/35925524/
3. Steinkellner, Hannes, Etzler, Julia, Gogoll, Laura, Brandau, Oliver, Laccone, Franco. 2014. Identification and molecular characterisation of a homozygous missense mutation in the ADAMTS10 gene in a patient with Weill-Marchesani syndrome. In European journal of human genetics : EJHG, 23, 1186-91. doi:10.1038/ejhg.2014.264. https://pubmed.ncbi.nlm.nih.gov/25469541/
4. Hu, Haifeng, Wang, Ying, Liu, Ying, Zhang, Tianyu, Dong, Bo. 2023. Comprehensive Analysis of ADAMTS Gene Family in Renal Clear Cell Carcinoma and ADAMTS10 Research Combining Magnetic Resonance Imaging. In Molecular biotechnology, 66, 3136-3149. doi:10.1007/s12033-023-00915-8. https://pubmed.ncbi.nlm.nih.gov/37861954/
5. Mularczyk, Ewa J, Singh, Mukti, Godwin, Alan R F, Kielty, Cay M, Baldock, Clair. . ADAMTS10-mediated tissue disruption in Weill-Marchesani syndrome. In Human molecular genetics, 27, 3675-3687. doi:10.1093/hmg/ddy276. https://pubmed.ncbi.nlm.nih.gov/30060141/
6. Wang, Lauren W, Kutz, Wendy E, Mead, Timothy J, Reinhardt, Dieter P, Apte, Suneel S. 2018. Adamts10 inactivation in mice leads to persistence of ocular microfibrils subsequent to reduced fibrillin-2 cleavage. In Matrix biology : journal of the International Society for Matrix Biology, 77, 117-128. doi:10.1016/j.matbio.2018.09.004. https://pubmed.ncbi.nlm.nih.gov/30201140/
7. Kuchtey, John, Olson, Lana M, Rinkoski, Tommy, Haines, Jonathan L, Kuchtey, Rachel W. 2011. Mapping of the disease locus and identification of ADAMTS10 as a candidate gene in a canine model of primary open angle glaucoma. In PLoS genetics, 7, e1001306. doi:10.1371/journal.pgen.1001306. https://pubmed.ncbi.nlm.nih.gov/21379321/
8. Wu, Hang-Jing, Mortlock, Douglas P, Kuchtey, Rachel W, Kuchtey, John. . Altered Ocular Fibrillin Microfibril Composition in Mice With a Glaucoma-Causing Mutation of Adamts10. In Investigative ophthalmology & visual science, 62, 26. doi:10.1167/iovs.62.10.26. https://pubmed.ncbi.nlm.nih.gov/34424262/