Reference SummaryWang TC, Gastroenterology 2000 Jan;118(1):36-47

Title

 Synergistic interaction between hypergastrinemia and helicobacter infection in a mouse model of gastric cancer

Authors

 Wang TC; Dangler CA; Chen D; Goldenring JR; Koh T; Raychowdhury R; Coffey RJ; Ito S; Varro A; Dockray GJ; Fox JG

Journal

 Gastroenterology

Volume

 118

Issue

 1

Year

 2000

Pages

 36-47

Abstract

 Background & Aims: Hypergastrinemia occurs frequently in association with acid suppression and Helicobacter infection, but its role in the progression to gastric atrophy and gastric cancer has not been well defined. Methods: The effects of hypergastrinemia, and possible synergy with Helicobacter felis infection, were investigated in insulin-gastrin (INS-GAS) transgenic mice. Results: INS-GAS mice initially showed mild hypergastrinemia, increased maximal gastric acid secretion, and increased parietal cell number but later progressed to decreased parietal cell number and hypochlorhydria. Development of gastric atrophy was associated with increased expression of growth factors, heparin-binding epidermal growth factor and transforming growth factor alpha. At 20 months of age, INS-GAS mice showed no evidence of increased enterochromaffin-like cell number, but instead exhibited gastric metaplasia, dysplasia, carcinoma in situ, and gastric cancer with vascular invasion. Invasive gastric carcinoma was observed in 6 of 8 INS-GAS mice that were >20 months old. Helicobacter felis infection of INS-GAS mice led to accelerated (

Links

 J:59575 – MGI References
10611152 – National Library of Medicine/PubMed

Strain Notes

Strain Note
FVB/NTac In mice 7-8 months old 'Histopathology showed all infected knockout mice had severe gastric atrophy. # of parietal cells per gland was reduced by 27% in infected FVB/N, 40% in uninfected knockout mice, and by 67% in infected knockout mice.'
Mice remained healthy for duration of experiment, regardless of treatment.
Mice were purchased from Taconic Farms.
FVB-Tg(Ins1-GAS)1Sbr In mice 7-8 months old 'Histopathology showed all infected knockout mice had severe gastric atrophy. # of parietal cells per gland was reduced by 27% in infected FVB/N, 40% in uninfected knockout mice, and by 67% in infected knockout mice.'
Mice display early and late phenotypes due to elevated gastrin levels. Early phase from 2-3 months of age shows increased gastric acid secretion consistent with early increases in parietal cell population. Late phase >5 months, show decline in gastric acid secretion and parietal cell number.
Study was halted due to illness observed in H. felis infected mice (for 7-8 month study).

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/NTac Stomach - Glandular carcinoma Stomach - Glandular

0
FVB/NTac Stomach - Glandular carcinoma
  • Helicobacter felis
 Stomach - Glandular

0
FVB-Tg(Ins1-GAS)1Sbr Stomach - Glandular carcinoma Stomach - Glandular

0 - 13
FVB-Tg(Ins1-GAS)1Sbr Stomach - Glandular carcinoma
  • Helicobacter felis
 Stomach - Glandular

25 - 100
FVB/NTac Stomach - Glandular dysplasia Stomach - Glandular

0
FVB-Tg(Ins1-GAS)1Sbr Stomach - Glandular dysplasia Stomach - Glandular

0 - 100
FVB-Tg(Ins1-GAS)1Sbr Stomach - Glandular dysplasia
  • Helicobacter felis
 Stomach - Glandular

observed - 100
FVB/NTac Stomach - Glandular hyperplasia - foveolar
  • Helicobacter felis
 Stomach - Glandular

observed
FVB/NTac Stomach - Glandular hyperplasia - foveolar Stomach - Glandular

0
FVB-Tg(Ins1-GAS)1Sbr Stomach - Glandular hyperplasia - foveolar Stomach - Glandular

observed - 100
FVB-Tg(Ins1-GAS)1Sbr Stomach - Glandular hyperplasia - foveolar
  • Helicobacter felis
 Stomach - Glandular

observed
FVB/NTac Stomach - Glandular metaplasia Stomach - Glandular

0
FVB-Tg(Ins1-GAS)1Sbr Stomach - Glandular metaplasia Stomach - Glandular

100
FVB-Tg(Ins1-GAS)1Sbr Stomach - Glandular metaplasia
  • Helicobacter felis
 Stomach - Glandular

observed