- Gastrin Knockout (GAS-KO) mice represent a significant model for investigating gastric cancer development through the complete absence of gastrin expression. These mice are engineered by disrupting the gastrin gene, resulting in a lack of both amidated and glycine-extended gastrin peptides, which fundamentally alters gastric acid secretion and mucosal development.
- The GAS-KO model demonstrates distinct morphological changes in the gastric mucosa. Without gastrin’s trophic effects, these mice exhibit reduced parietal cell numbers and impaired acid secretion, leading to hypochlorhydria. The gastric mucosa shows marked alterations, including reduced thickness, altered cellular composition, and compromised barrier function, creating a unique environment for studying gastric pathology.
- These mice are particularly valuable for investigating the role of gastrin in Helicobacter infection and inflammation. When infected with H. pylori, GAS-KO mice show different responses compared to wild-type mice, with altered inflammatory patterns and bacterial colonization rates. This helps researchers understand gastrin’s role in host defense and bacterial-induced pathogenesis.
- The absence of gastrin in these mice leads to significant changes in cellular differentiation and proliferation within the gastric mucosa. They display altered expression of various growth factors and cytokines, providing insights into gastrin’s regulatory role in normal gastric physiology and cancer development. The model is especially useful for studying the impact of gastrin deficiency on stem cell dynamics and cellular transformation.
- GAS-KO mice have proven instrumental in elucidating gastrin’s role in both protective and pathogenic processes. They help researchers understand how gastrin deficiency affects susceptibility to gastric injury, inflammation, and carcinogenesis. The model continues to be valuable for investigating therapeutic strategies targeting gastrin-dependent pathways and for developing treatments for gastric cancer and other gastrointestinal disorders.
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