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Analysis for factors that regulate mast cell number by using mutant mice at mi locus

mi位点突变小鼠肥大细胞数量调节因素分析

基本信息

批准号：
15590341
负责人：
MORII Eiichi
金额：
$ 2.18万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590341/
关键词：
mast cells MITF mutant mice number 皮膚分化環境転写因子 KIT SCF

项目摘要

MITF is encoded at the mouse mi locus. Mutant mice at mi locus show abnormalities of mast cell phenotypes, indicating that MITF is impotant for the transcription of mast cell specific genes. In addition to the abnormality of phenotypes, the number of mast cells decreased in the mutant mice at the mi locus. This suggested that MITF regulated the number of mast cells. Here, we studied factors regulating mast cell number by using mutant mice at the mi locus.The tg/tg mice that lacked the expression of MITF showed the decrease of dermal mast cell number. We found that the decrease of mast cell number was observed orry when the tg/tg mace possessed C57BL/6 genetic background. The tg/tg mice possessiig WB genetic background did not show the decrease of dermal mast cell number. With the genetic mapping method, we identified the factor that increased mast cell number in the absence of MITF. This fad was the soluble KitL. KitL is an important growth factor for the development of mast cells. The expression level of the receptor far KitL was lower in tg/tg mace than in normal mice. This suggested that the soluble form of KitL was difficult to be produced in C57BL/6-tg/tg mice, and that the dermal mast cells could not Proliferate.We also showed that MITF was important for the synthesis of chemical mediator ; prostaglandin D2, and that the newly-identified adhesion molecule, SgIGSF, was necessary far the development of mast cells in the peritoneal cavity.

MITF在小鼠mi基因座处编码。突变小鼠肥大细胞表型异常，提示MITF对肥大细胞特异性基因的转录起重要作用。除了表型异常外，mi基因突变小鼠的肥大细胞数量也减少。这表明MITF调节肥大细胞的数量。在此，我们使用mi基因突变小鼠研究了肥大细胞数量的调节因素，MITF表达缺失的tg/tg小鼠表现出真皮肥大细胞数量的减少。结果发现，具有C57 BL/6遗传背景的tg/tg mace细胞肥大细胞数明显减少。具有WB遗传背景的tg/tg小鼠皮肤肥大细胞数无明显减少。通过遗传作图的方法，我们确定了在MITF缺失的情况下肥大细胞数量增加的因素。这股潮流就是可溶性KitL。KitL是肥大细胞发育的重要生长因子。在tg/tg mace小鼠中，KitL受体的表达水平低于正常小鼠。这表明C57 BL/6-tg/tg小鼠皮肤中很难产生可溶性KitL，皮肤肥大细胞不能粘附，MITF对化学介质前列腺素D2的合成起重要作用，而新发现的粘附分子SgIGSF对腹腔肥大细胞的发育是必需的。