Making and analysis of a transjenic model of Mastocytosis and urticalia pigmentosa by the forced expression of steel factor in the skin.

皮肤钢因子强制表达肥大细胞增多症和色素性荨麻疹跨肾模型的制作和分析。

• 批准号: 09670880
• 负责人: KUNISADA Takahiro
• 金额: $ 2.11万
• 依托单位: TOTTORI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670880/
• 关键词: steel factor; transgenic mouse; mast cell; pigment cell; mastocytosis; 色素性じん麻疹症; サイトケラチンプロモーター

Transgenic mouse models for mastocytosis and urticalia pigmentosa were made by the forced expression of steel factor in the skin and the following results were obtained.1. Mastocytosis was reproducibly expressed by the expression of soluble steel factor in the basal cells of skin. Membrane-bound type steel factor developed only melanosis, but not any signs of mastocytosis.2. The mice that had shown mastocytosis were all developed melanocyte overgrowth in the skin, representing the symptom of urticalia pigmentosa, most common types of mastocytosis.3. In vivo administration of blocking antibody of steel factor-c-Kit signaling completely abolished the maintenance of mast cells and melanocytes, indicating that increase of these cells were caused by the expression of the steel transgene.4. Our mastocytosis models showed quicker and more extensive inflammatory response. This further implies that the model mice will be useful for the study of the roles of mast cells in inflammation.

通过在皮肤中强制表达钢因子，建立肥大细胞增多症和色素性荨麻疹转基因小鼠模型，得到以下结果： 1．肥大细胞增多症通过皮肤基底细胞中可溶性钢因子的表达而可重复地表达。膜结合型钢因子只出现黑变病，而没有肥大细胞增多症的迹象。2．出现肥大细胞增多症的小鼠均出现皮肤黑色素细胞过度生长，表现为色素性荨麻疹的症状，这是肥大细胞增多症最常见的类型。 3．体内给予steel因子-c-Kit信号阻断抗体后，肥大细胞和黑素细胞的维持完全消失，表明这些细胞的增加是由steel转基因的表达引起的。4．我们的肥大细胞增多症模型显示出更快、更广泛的炎症反应。这进一步意味着模型小鼠将有助于研究肥大细胞在炎症中的作用。

项目成果

Ogawa, M.: "Flt3/Flk-2 and c-kit are not essential for the proliferation of B lymphoid progenitor cells in the bone marrow of the adult mouse." Exp.Hematol.26. 478-488 (1998)

Okawa, M.：“Flt3/Flk-2 和 c-kit 对于成年小鼠骨髓中 B 淋巴祖细胞的增殖不是必需的。”

Yamazaki, H.: "Tooth-specific expression conferred by the regulatory sequences of rat dentin sialoprotein 2 gene in transgenic mice." Biochem.Biophys.Res.Commum.(in press).

Yamazaki, H.：“转基因小鼠中大鼠牙本质唾液蛋白 2 基因的调控序列赋予牙齿特异性表达。”

Kunisada, T.: "Hyperproliferation of melanocytes ant mast cells caused by targeting expression of Steel factor to tne skin." J.Exp.Med.(in press).

Kunisada, T.：“通过将钢铁因子靶向表达到皮肤而引起黑色素细胞和肥大细胞的过度增殖。”

Yamazaki, H.: "Promotion of early osteoclastgenesis and B lymphoiesis in the bone marrow of transgenic rats with the env-pX gene of human T-cell lymphotropic virus type I." Oncogene. 17. 2955-2960 (1998)

Yamazaki, H.：“带有人类 T 细胞嗜淋巴细胞病毒 I 型 env-pX 基因的转基因大鼠骨髓中早期破骨细胞生成和 B 淋巴细胞的促进作用。”

Miyamoto,A.: "Establishment and characterization of an immortal macrophage-like cell line inducible to differentiate to osteoclasts." Biochem.Biophys.Res.Commum.242. 703-709 (1998)

Miyamoto,A.：“可诱导分化为破骨细胞的永生巨噬细胞样细胞系的建立和表征。”