| Budget Amount *help |
¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1996: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥5,400,000 (Direct Cost: ¥5,400,000)
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| Research Abstract |
Chronic atrophic gastritis is thought be a potential pre-stage of gastric cancer. It is well known that infection of Helicobacter pylori in stomach or auto-immune mechanisms again gastric parietal cells cause atrophic change of gastric mucous, however, the precise mechanism of getting gastric atrophy is not clear. On the other hand, gastrin levels in the serum of atrophic gastritis patients are proved to be higher than normal subjects.
To investigate the mechanisms how gastric chronic atrophy occurs, we first tried to establish transgenic mice those serum gastrin levels are consistently higher than normal mice. Because that gastrin is not stable in living animals (half life of gastrin was estimated about 8 min.) and that processing steps of gastrin from its precursor is acheved in limited kinds of cells, to establish model mice that show consistently high gastrin level in serum was not easy. Thus, previously established high gastrin level models were not sufficient for our purpose.
Furin
… More
is one of proprotein-processing endoproteases and known to be expressed most types of tissues. We made chimeric DNA that has beta actin promoter and mutated gastrin cDNA.This mutation of gastrin cDNA was made so that transcripts from this mutated cDNA could be recognized by furin.
After introduction of this chimeric DNA into mice, we checked serum gastrin level of these mice. They showed three to ten folds higher levels of serum gastrin. Now we are investigating the characteristic of these mice.
Next, we tried to establish culture cell lines of mouse gastric parietal cells to investigate why gastric atrophic change occurs after depletion of parietal cells. To achieve this purpose, newly established cell lines must be highly purified and keep the characters differentiated parietal cells have.
To this purpose, we made a chimeric DNA.In this DNA,temperature sensitive SV40 large T antigen cDNA was settled under control of parietal cell specific H/K ATPase beta subunit promoter. This DNA was introduced into mice and expression of SV40 large T antigen was checked by Southern blot. Now we are trying to establish parietal cell lines from these mice. Less
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