Generation and Application of Inducible Chimeric RNA ASTN2-PAPPAas Knockin Mouse Model

Cells. 2022 Jan 14;11(2):277. doi: 10.3390/cells11020277.

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.

Keywords: A-PaschiRNA; cancer; fusion RNA; genetically engineered mouse model; knockin mouse; transcription-induced chimeric RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Nitroquinoline-1-oxide
  • Animals
  • Body Weight / drug effects
  • Carcinogens / toxicity
  • Disease Models, Animal
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Gene Knock-In Techniques*
  • Genotype
  • Mice
  • Mice, Inbred C57BL
  • Mouse Embryonic Stem Cells / drug effects
  • Mouse Embryonic Stem Cells / metabolism
  • Quinolones
  • RNA, Antisense / genetics*
  • Tamoxifen / pharmacology

Substances

  • 4-nitroquinolone-1-oxide
  • Carcinogens
  • Quinolones
  • RNA, Antisense
  • Tamoxifen
  • 4-Nitroquinoline-1-oxide