Rong Li1, Jinxin Miao1, Alexandru-Flaviu Tabaran2, M. Gerard O’Sullivan2, Kyle J Anderson3, Patricia M Scott3, Zhongde Wang1, Robert T Cormier3
1Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, USA
2Veterinary Diagnostic Laboratory, College of Veterinary Medicine, University of Minnesota; Comparative Pathology Shared Resource, Masonic Cancer Center, University of Minnesota, Duluth, MN, USA
3Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN, USA
DOI: 10.4103/jcar.JCar_5_18
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.
Keywords: Golden Syrian hamster, KCNQ1, tumor suppressor