Funktion des Laminin-bindenden Integrins alpha7beta1 während der Embryonalentwicklung (Functional analysis of the Laminin-binding Integrin alpha7beta1 during Embryonic Development)

胚胎发育过程中层粘连蛋白结合整合素α7β1的功能分析

• 批准号: 5250418
• 负责人: Professorin Dr. Ulrike Mayer
• 金额: --
• 依托单位: School of Biological Sciences
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2000
• 资助国家: 德国
• 起止时间: 1999-12-31 至 2002-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5250418?language=en
• 关键词: Funktion; des; Laminin; bindenden; Integrins

Integrins are heterodimeric cell surface receptors, consisting of an a- and a ß-chain which are non-covalently associated. It is well recognised that they influence cellular behaviour, such as adhesion, migration, differentiation and polarisation of cells. The ß1 integrin family represent the biggest class of cell surface receptors for extracellular matrix proteins. The a7ß1 integrins ist one of twelve currently known members. a7ß1 has been identified as specific receptor for the basement membrane protein laminin and is mainly expressed in skeletal and cardiac muscle. Targeted inactivation of the integrin a7 gene in the germline of mice has shown, that mice, deficient for the a7ß1 integrin develop a new form of muscular dystrophy at adult stages. However, the analysis demonstrated that according to the Mendelian ratio only 50 % of the a7-deficient animals live to term and survive. The first analysis indicates that nonsurviving homozygous mutant mice die during early gestational stages, where the expression pattern of the integrin a7 subunit is only poorly characterised. Therefore, it is planned to define the expression pattern of the integrin a7 subunit, thus allowing the identication of the molecular defects underlying embryonic lethality due to integrin a7 deficiency in the frame of this proposal.

整合素是异二聚体细胞表面受体，由非共价连接的α链和β链组成。众所周知，它们影响细胞行为，例如细胞的粘附、迁移、分化和极化。 ß1 整合素家族代表细胞外基质蛋白的最大一类细胞表面受体。 a7ß1 整合素是目前已知的十二个成员之一。 a7ß1已被确定为基底膜蛋白层粘连蛋白的特异性受体，主要在骨骼肌和心肌中表达。小鼠种系中整合素 a7 基因的定向失活表明，缺乏 a7ß1 整合素的小鼠在成年阶段会出现一种新形式的肌营养不良症。然而，分析表明，根据孟德尔比率，只有 50% 的 a7 缺陷动物能够足月存活。第一个分析表明，未存活的纯合突变小鼠在妊娠早期死亡，此时整合素 a7 亚基的表达模式的特征很少。因此，计划定义整合素a7亚基的表达模式，从而在该提案的框架内鉴定由于整合素a7缺陷而导致胚胎致死的分子缺陷。