| Project/Area Number |
22791291
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Kumamoto University |
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Principal Investigator |
OHMURAYA Masaki 熊本大学, 大学院・先導機構, 特任助教 (60398229)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 膵臓外科学 / 遺伝子改変マウス / 慢性膵炎モデルマウス / SPINK1/Spink3 / 慢性膵炎 / X染色体不活性化 / SPINK1/Sink3 / 膵癌 / 膵癌モデルマウス |
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| Research Abstract |
The mutations of serine protease inhibitor Kazal type 1(SPINK1) are associated with chronic pancreatitis(CP). We previously showed that deletion of Spink3, the mouse homologue of SPINK1, causes pancreatitis-like changes in the mouse. The aim of this study was to rescue the Spink3-/-phenotype by generating Spink3-/-mice with knockin SPINK1.(Methods) We placed CAG-SPINK1 gene(SP1) into X chromosome. X-inactivation is a process whereby one of the two copies of the X chromosome present in female mammals is inactivated. By utilizing X-inactivation, we were able to create mice in which SPINK1 level was partially, but not completely, reduced. The SP1 knockin mice were crossed to Spink3+/-mice.(Results) The pancreas of Spink3-/-XSP1/+mice at birth contained both normal and degenerated acinar cells, with accumulation of autophagic vacuoles. The Spink3-/-XSP1/+mice developed pathologic features of human CP, including loss of acinar cells and fibrosis with activated stellate cells. Older mice displayed acinar-ductal metaplasia and prominent expression of proto-oncogenes Egfr, Her2, and Ras.(Conclusions) The results indicate that CP trigger factors promoting pancreatic cancer development.
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