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

MITF是在鼠标微卫星位点编码的。Mi位点突变小鼠表现为肥大细胞表型异常，提示MITF对肥大细胞特异性基因的转录具有重要作用。除表型异常外，突变小鼠除表型异常外，还可见肥大细胞数量减少。提示MITF对肥大细胞的数量有调节作用。在此，我们利用MITF基因突变小鼠研究了肥大细胞数量的调控因素。MITF表达缺失的TG/TG小鼠真皮肥大细胞数量减少。我们发现，当TG/TG MACE具有C57BL/6遗传背景时，肥大细胞数量也会减少。具有WB遗传背景的Tg/Tg小鼠未见真皮肥大细胞数量减少。通过遗传作图的方法，我们确定了在没有MITF的情况下肥大细胞数量增加的因素。这一时尚就是可溶性的KitL。KitL是肥大细胞发育的重要生长因子。TG/TG MACE小鼠Far KitL受体的表达水平低于正常小鼠。提示在C57BL/6-TG/TG小鼠体内很难产生可溶性KitL，真皮肥大细胞不能增殖，MITF对化学介质前列腺素D2的合成起重要作用，新发现的黏附分子SgIGSF对腹膜肥大细胞的发育是必需的。

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.