Generation of filggrin-deficient mice and analysis o differentiation and apoptosis of keratinocytes

丝蛋白缺陷小鼠的产生及角质形成细胞的分化和凋亡分析

• 批准号: 11670816
• 负责人: NEGISHI Izumi
• 金额: $ 2.3万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670816/
• 关键词: filaggrin; knockout mouse; keratinocyte; apoptosis

It has been reported that filaggrin may be involved in the terminal differentiation (apoptosis) of keratinocytes. In order to study of keratinocyte differentiation in vivo, we are planning to generate filaggrin-deficient mice. Filaggrin is composed of approximately 320 amino acids and the unit of profilaggrin, which consists of multiple filaggrin-repeats. To generate filaggrin-deficient mice, we need to disrupt the region containing the initiation codon of the profilaggrin gene rather than the coding region of filaggrin. We succeeded to obtain a BAC clone containing the mouse profilaggrin gene with a human profilaggrin cDNA as a probe. We have subloned the important regions of this gene to design a targeting vector. At present, filaggrin^<+/-> ES cells are under construction.

有报道称，丝聚蛋白可能参与角质形成细胞的终末分化（凋亡）。为了研究角质形成细胞在体内的分化，我们计划产生丝状蛋白缺陷小鼠。聚丝蛋白由大约320个氨基酸和聚丝蛋白原的单位组成，聚丝蛋白原的单位由多个聚丝蛋白重复序列组成。为了产生聚丝蛋白缺陷小鼠，我们需要破坏包含聚丝蛋白原基因的起始密码子的区域，而不是聚丝蛋白的编码区域。我们成功地获得了一个BAC克隆含有小鼠微丝聚集蛋白原基因与人微丝聚集蛋白原cDNA作为探针。我们对该基因的重要区域进行了亚克隆，设计了靶向载体。目前，聚丝蛋白（filaggrin）^<+/-> ES细胞正在构建中。