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