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

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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.