A novel cancer syndrome caused by KCNQ1-deficiency in the golden Syrian hamster.

Q1 Environmental Science Journal of Carcinogenesis Pub Date : 2018-10-10 eCollection Date: 2018-01-01 DOI:10.4103/jcar.JCar_5_18
Rong Li, Jinxin Miao, Alexandru-Flaviu Tabaran, M Gerard O'Sullivan, Kyle J Anderson, Patricia M Scott, Zhongde Wang, Robert T Cormier
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Abstract

Background: The golden Syrian hamster is an emerging model organism. To optimize its use, our group has made the first genetically engineered hamsters. One of the first genes that we investigated is KCNQ1 which encodes for the KCNQ1 potassium channel and also has been implicated as a tumor suppressor gene.

Materials and methods: We generated KCNQ1 knockout (KO) hamsters by CRISPR/Cas9-mediated gene targeting and investigated the effects of KCNQ1-deficiency on tumorigenesis.

Results: By 70 days of age seven of the eight homozygous KCNQ1 KOs used in this study began showing signs of distress, and on necropsy six of the seven ill hamsters had visible cancers, including T-cell lymphomas, plasma cell tumors, hemangiosarcomas, and suspect myeloid leukemias.

Conclusions: None of the hamsters in our colony that were wild-type or heterozygous for KCNQ1 mutations developed cancers indicating that the cancer phenotype is linked to KCNQ1-deficiency. This study is also the first evidence linking KCNQ1-deficiency to blood cancers.

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金色叙利亚仓鼠 KCNQ1 缺陷导致的新型癌症综合征
背景:金色叙利亚仓鼠是一种新兴的模式生物。为了更好地利用它,我们小组制作了第一批基因工程仓鼠。我们首先研究的基因之一是 KCNQ1,它编码 KCNQ1 钾通道,也被认为是肿瘤抑制基因:我们通过CRISPR/Cas9介导的基因打靶产生了KCNQ1基因敲除(KO)仓鼠,并研究了KCNQ1缺失对肿瘤发生的影响:在本研究中使用的 8 只同源 KCNQ1 KO 仓鼠中,有 7 只在 70 天大时开始出现不适症状,在解剖时,7 只患病仓鼠中有 6 只出现了明显的癌症,包括 T 细胞淋巴瘤、浆细胞瘤、血管肉瘤和疑似髓性白血病:结论:在我们的仓鼠群中,野生型或 KCNQ1 基因突变杂合子仓鼠均未患癌症,这表明癌症表型与 KCNQ1 基因缺陷有关。这项研究也是将 KCNQ1 缺失与血癌联系起来的首个证据。
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来源期刊
Journal of Carcinogenesis
Journal of Carcinogenesis Environmental Science-Health, Toxicology and Mutagenesis
CiteScore
7.50
自引率
0.00%
发文量
0
审稿时长
15 weeks
期刊介绍: Journal of Carcinogenesis considers manuscripts in many areas of carcinogenesis and Chemoprevention. Primary areas of interest to the journal include: physical and chemical carcinogenesis and mutagenesis; processes influencing or modulating carcinogenesis, such as DNA repair; genetics, nutrition, and metabolism of carcinogens; the mechanism of action of carcinogens and modulating agents; epidemiological studies; and, the formation, detection, identification, and quantification of environmental carcinogens. Manuscripts that contribute to the understanding of cancer prevention are especially encouraged for submission
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