| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
The transcription factor Foxl1 is specifically expressed in the mesenchyme of digestive organs. We generated Foxl1 knockout (KO) mice and found that loss oFoxl1f led to differentiation of oxynticopeptic-like cells which have features of both hydrochloric acid-secreting parietal and pepsinogen-secreting chief cells, and which are only found in stomachs of lower vertebrates but not in those of mammals. Thus expression oFoxl1f seems to play a key role in the differentiation of parietal and chief cells during evolution of mammals from reptiles. To elucidate the mechanism of action oFoxl1f, the gene expression profiles in KO and wild type(WT) gastro-intestinal tissues were compared.
We found that the expression level of syntaxin3, VAMP2, Rab3a and ARF6 proteins was not almost equivalent between WT and KO mic, shereas that of SNAP25 decreased in KO mice. Defect in acid secretion from KO parietal cells seems to result form the combined effect of the impairment in membrane fusion between tubulovesicles and secretory canaliculi due to reduced SNAP25 and a decrease in the expression of H, K-ATPase subunits for proton excretion.
The epithelial hyperplasias are found both in gastric and intestinal tissues in KI mice. Thus gene expression profiles were also compared in intestinal tissues. We found that in fully differentiated as well as developing small intestine, lack of fff resulted in ectopic and increased expression of EphB2 and EphB2, which, in collaboration with their ligand EphrinB1, have been demonstrated to be involved in regulating epithelial cell positioning along the crypt-villus axis. Furthermore, we detected an increase in Wnt4, Wnt11 and Glypican3 in mesenchyme, and an increase of Syndecan2 in epithelia of KO mice. These results altered expression of extracellular matrixes.
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