Generation and Application of Inducible Chimeric RNA <i>ASTN2-PAPPA</i><sub>as</sub> Knockin Mouse Model
Yichen Luo,
Liang Du,
Zhimeng Yao,
Fan Liu,
Kai Li,
Feifei Li,
Jianlin Zhu,
Robert P. Coppes,
Dianzheng Zhang,
Yunlong Pan,
Shegan Gao,
Hao Zhang
Affiliations
Yichen Luo
Institute of Precision Cancer Medicine and Pathology, School of Medicine and Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China
Liang Du
Department of Biomedical Sciences of Cells & Systems, Section Molecular Cell Biology and Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, The Netherlands
Zhimeng Yao
Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China
Fan Liu
Institute of Precision Cancer Medicine and Pathology, School of Medicine, Jinan University, Guangzhou 510632, China
Kai Li
Institute of Precision Cancer Medicine and Pathology, School of Medicine, Jinan University, Guangzhou 510632, China
Feifei Li
Department of Oncology, People’s Hospital of Leshan, Leshan 614099, China
Jianlin Zhu
Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China
Robert P. Coppes
Department of Biomedical Sciences of Cells & Systems, Section Molecular Cell Biology and Radiation Oncology, University Medical Center Groningen, University of Groningen, 9700 AD Groningen, The Netherlands
Dianzheng Zhang
Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, 4170 City Avenue, Philadelphia, PA 19131, USA
Yunlong Pan
Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China
Shegan Gao
Henan Key Laboratory of Cancer Epigenetics, College of Clinical Medicine, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang 471000, China
Hao Zhang
Department of General Surgery, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou 510632, China
Chimeric RNAs (chiRNAs) play many previously unrecognized roles in different diseases including cancer. They can not only be used as biomarkers for diagnosis and prognosis of various diseases but also serve as potential therapeutic targets. In order to better understand the roles of chiRNAs in pathogenesis, we inserted human sequences into mouse genome and established a knockin mouse model of the tamoxifen-inducible expression of ASTN2-PAPPA antisense chimeric RNA (A-PaschiRNA). Mice carrying the A-PaschiRNA knockin gene do not display any apparent abnormalities in growth, fertility, histological, hematopoietic, and biochemical indices. Using this model, we dissected the role of A-PaschiRNA in chemical carcinogen 4-nitroquinoline 1-oxide (4NQO)-induced carcinogenesis of esophageal squamous cell carcinoma (ESCC). To our knowledge, we are the first to generate a chiRNA knockin mouse model using the Cre-loxP system. The model could be used to explore the roles of chiRNA in pathogenesis and potential targeted therapies.
