Protein Kinase A (PKAc alpha ) regulates gastric homeostasis and preneoplastic lesions

We generated a novel Six2-Cre+/-PKAcaRfl/wt (CA-PKA) CA-PKA mouse in which expression of constitutive-active PKAcaR was induced in gastric mesenchyme progenitors. CA-PKA mice showed disruption of gastric homeostasis characterized by aberrant mucosal development and epithelial hyperproliferation; ultimately developing multiple features of gastric corpus preneoplasia including decreased parietal cells, mucous cell hyperplasia, spasmolytic peptide expressing metaplasia (SPEM) with intestinal characteristics and dysplastic and invasive cystic glands. Our results show that constitutively active PKAcaR in the stomach mesenchyme nonautonomously disrupts gastric homeostasis characterized by increased epithelial proliferation and aberrant epithelial maldevelopment, ultimately leading to gastric preneoplasia. To identify differentially expressed genes mRNA sequencing was performed on samples isolated from the corpus region of control and mutant mice. Four biological replicates were analyzed from control and mutant mice.