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

整合素是细胞表面的异二聚体受体，由非共价结合的a-链和？-链组成。众所周知，它们会影响细胞的行为，如细胞的黏附、迁移、分化和极化。1整合素家族是细胞外基质蛋白最大的细胞表面受体。A7？1整合素是目前已知的12个成员之一。A7？1是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。小鼠胚系中整合素A7基因的定向失活表明，缺乏A7？1整合素的小鼠在成年阶段会发展成一种新的肌营养不良症。然而，分析表明，根据孟德尔比率，只有50%的A7缺乏的动物能存活并存活下来。第一个分析表明，死亡的纯合子突变小鼠在早期妊娠阶段死亡，整合素A7亚单位的表达模式只是一个很差的特征。因此，计划定义整合素A7亚单位的表达模式，从而在本提案的框架内识别由于整合素A7缺陷而导致的胚胎致死性的分子缺陷。

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.