Effects of a gastrin receptor antagonist (NTZ, previously named YF) on the gastric corpus mucosa of HKATPase betasubunit knockout (KO) mice

Purpose: the effects of a gastrin receptor antagonist has been studies in patients with gastrin neuroendocrine (NE) tumours due to hypergastrinemia. This mouse model of hypergastrinemia is a model for studying long term acid inhibition, including NE hyperplasia and formation of Spasmolytic polypeptide expressing metaplasia (SPEM), a proposed premalignant alteration of the stomach. Methods: RNA was isolated from the oxyntic mucosa. RNA was sequenced using standard Illumina protocols on a NextSeq 500 instrument. Results: NTZ reduced oxyntic mucosal hypertropohy and stomach weight. Neuroendocrine cell hyperplasia and NE markers were also reduced. Spasmolytic polypeptide expressing metaplasia (SPEM) was expressed in KO mice and was not affected by the gastrin receptor antagonist. Conclusions: The gastrin receptor antagonist YF reduced gastric corpus mucosal hypertrophy and NE cell hyperplasia in HKATPase KO mice, but did not affect SPEM or SPEM related genes. Overall design: Gastric corpus mRNA profiles of 13 months old WT and KO mice, given YF or vehicle (PEG) were generated by sequencing using an Illumina NextSeq 500 instrument to examine the effect of genotype and NTZ.