Analysis of Knockout Mice Reveals an Essential Role for Gastric Sulfomucins in Preventing Gastritis Cystica Profunda.

Gastric adenocarcinoma cells secrete sulfomucins, but their role in gastric tumorigenesis remains unclear. To address that question, we generated / double-knockout (DKO) mice by crossing knockout (KO) mice, which spontaneously develop gastric adenocarcinoma, with KO mice, which are deficient in the sulfotransferase GlcNAc6ST-2. / DKO mice lack gastric sulfomucins but developed gastric adenocarcinoma. Unexpectedly, severe gastric erosion occurred in / DKO mice at as early as 3 weeks of age, and with aging these lesions were accompanied by gastritis cystica profunda (GCP). , and transcripts in gastric mucosa of 5-week-old / DKO mice exhibiting both hyperplasia and severe erosion were significantly upregulated relative to age-matched KO mice, which showed hyperplasia alone. However, upregulation of these genes disappeared in 50-week-old / DKO mice exhibiting high-grade dysplasia/adenocarcinoma and GCP. Moreover, and were downregulated in / DKO mice relative to age-matched KO mice exhibiting adenocarcinoma alone. These combined results indicate that the presence of sulfomucins prevents severe gastric erosion followed by GCP in KO mice by transiently regulating a set of inflammation-related genes, , and at 5 weeks of age, although sulfomucins were not directly associated with gastric cancer development.