Li Rong, Miao Jinxin, Tabaran Alexandru-Flaviu, O'Sullivan M Gerard, Anderson Kyle J, Scott Patricia M, Wang Zhongde, Cormier Robert T
Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, USA.
Veterinary Diagnostic Laboratory, College of Veterinary Medicine, University of Minnesota, Duluth, MN, USA.
J Carcinog. 2018 Oct 10;17:6. doi: 10.4103/jcar.JCar_5_18. eCollection 2018.
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 which encodes for the KCNQ1 potassium channel and also has been implicated as a tumor suppressor gene.
We generated knockout (KO) hamsters by CRISPR/Cas9-mediated gene targeting and investigated the effects of KCNQ1-deficiency on tumorigenesis.
By 70 days of age seven of the eight homozygous 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.
None of the hamsters in our colony that were wild-type or heterozygous for mutations developed cancers indicating that the cancer phenotype is linked to -deficiency. This study is also the first evidence linking KCNQ1-deficiency to blood cancers.
金黄叙利亚仓鼠是一种新兴的模式生物。为了优化其应用,我们团队培育出了首批基因工程仓鼠。我们最早研究的基因之一是 ,它编码KCNQ1钾通道,并且也被认为是一种肿瘤抑制基因。
我们通过CRISPR/Cas9介导的基因靶向技术培育出了 基因敲除(KO)仓鼠,并研究了KCNQ1缺陷对肿瘤发生的影响。
在本研究中使用的8只纯合 基因敲除仓鼠中,到70日龄时,有7只开始出现不适迹象,尸检时,7只患病仓鼠中有6只出现了可见的癌症,包括T细胞淋巴瘤、浆细胞瘤、血管肉瘤和疑似髓系白血病。
我们群体中野生型或 基因突变杂合的仓鼠均未发生癌症,这表明癌症表型与 基因缺陷有关。本研究也是将KCNQ1缺陷与血癌联系起来的首个证据。