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

整合素是异二聚体细胞表面受体，由非共价结合的a-链和ß-链组成。众所周知，它们影响细胞行为，如粘附、迁移、分化和细胞极化。整合素家族代表了细胞外基质蛋白的最大一类细胞表面受体。a7ß1整合蛋白是目前已知的12个成员之一。A7ß1已被鉴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。在小鼠种系中靶向灭活整合素a7基因表明，缺乏a7ß1整合素的小鼠在成年期会出现一种新的肌肉萎缩症。然而，分析表明，根据孟德尔比率，只有50%的a7缺陷动物活到足月并存活下来。第一项分析表明，未存活的纯合子突变小鼠在妊娠早期死亡，此时整合素7亚基的表达模式特征不明显。因此，我们计划确定整合素7亚基的表达模式，从而在本提案的框架内确定整合素7缺乏导致胚胎致死的分子缺陷。

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.