Specific ablation of the nidogen-binding site in the laminin gamma 1 chain interferes with kidney and lung development

Willem, M., Miosge, N., Halfter, W., Smyth, N., Jannetti, I., Burghart, E., Timpl, R. and Mayer, U. (2002) Specific ablation of the nidogen-binding site in the laminin gamma 1 chain interferes with kidney and lung development. Development, 129, 2711-2722.

Abstract

Basement membrane assembly is of crucial importance in the development and function of tissues and during embryogenesis. Nidogen 1 was thought to be central in the assembly processes, connecting the networks formed by collagen type IV and laminins, however, targeted inactivation of nidogen 1 resulted in no obvious phenotype. We have now selectively deleted the sequence coding for the 56 amino acid nidogen-binding site, {gamma}1III4, within the Lamc1 gene by gene targeting. Here, we show that mice homozygous for the deletion die immediately after birth, showing renal agenesis and impaired lung development. These developmental defects were attributed to locally restricted ruptures in the basement membrane of the elongating Wolffian duct and of alveolar sacculi. These data demonstrate that an interaction between two basement membrane proteins is required for early kidney morphogenesis in vivo.

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