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Generation and Application of Inducible Chimeric RNA ASTN2-PAPPAas Knockin Mouse Model
Yichen Luo1, Liang Du2,3, Zhimeng Yao4,5
1Institute 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.
Abstract:
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.
Insights
Researchers developed a novel mouse model for studying chimeric RNAs (chiRNAs) and their role in cancer. This model allows for the investigation of chiRNA functions in disease pathogenesis and potential therapeutic strategies.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Chimeric RNAs (chiRNAs) are increasingly recognized for their roles in various diseases, including cancer.
- chiRNAs hold potential as diagnostic biomarkers and therapeutic targets.
- Understanding chiRNA roles in pathogenesis is crucial for developing new treatments.
Purpose of the Study:
- To establish a novel inducible mouse model for studying the function of a specific chimeric RNA, ASTN2-PAPPA antisense chimeric RNA (A-P aschiRNA).
- To investigate the role of A-P aschiRNA in the development of esophageal squamous cell carcinoma (ESCC) using a chemical carcinogen model.
Main Methods:
- Generation of a tamoxifen-inducible knockin mouse model expressing A-P aschiRNA using the Cre-loxP system.
- Assessment of the physiological and biochemical indices in the A-P aschiRNA knockin mice.
- Induction of esophageal squamous cell carcinoma (ESCC) using 4-nitroquinoline 1-oxide (4NQO) in the established mouse model.
Main Results:
- The A-P aschiRNA knockin mice showed no apparent abnormalities in growth, fertility, or standard health indicators.
- The developed mouse model successfully allowed for the investigation of A-P aschiRNA's role in 4NQO-induced ESCC.
- This study represents the first instance of a chiRNA knockin mouse model generated via the Cre-loxP system.
Conclusions:
- The novel A-P aschiRNA knockin mouse model is a valuable tool for studying chiRNA functions in disease.
- This model can facilitate research into the pathogenesis of diseases involving chiRNAs and aid in the development of targeted therapies.
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