Study on gastritis, metaplasia, and gastric cancer using new mice models of gastritis and carcinogenesis

• Project/Area Number: 26860493
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: Kinoshita Hiroto 東京大学, 医学部附属病院, 特任臨床医 (50645322)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 胃癌マウスモデル / 胃炎症発癌モデル

Outline of Final Research Achievements

For the purpose of stomach epithelium-specific gene modification, we newly generated Tff1-Cre mouse lines using the BAC transgenic technique. To elucidate the site of Tff1-Cre transgene expression, we crossed Tff1-Cre mice to Rosa-EYFP reporter mice, and analyzed the tissues with immunohistochemistry. Tff1-Cre positive cells were detected not only in pit and pre-pit cells but also in part of neck and chief cells. Tff1-Cre expression was not detected in parietal cells or endocrine cells. Next we crossed Tff1-Cre mice to LSL-KrasG12D mice. Tff1-Cre; LSL-KrasG12D mice displayed foveolar hyperplasia, oxyntic atrophy, and Alcian blue-positive mucous metaplasia at the age of 3 months. Now we are planning to cross Tff1-Cre mice to several other genetically modified mouse lines in order to study the mechanisms of gastric metaplasia and carcinogenesis.