Analysis of skin of nidogen deficient mouse models

Basement membranes (BMs) are produced by complex interactions of laminins, collagen IV, perlecan and nidogen. Nidogen represents a small family of related proteins with two mammalian isoforms nidogen 1 and 2. Nidogens are ubiquitous BM components that have been proposed to play a key role for BM assembly. However, neither nidogen 1 nor nidogen 2 deficient mice showed BM defects suggesting overlapping functions of the two isoforms for the formation of BMs. Nidogen double null mice showed that this is indeed 1the case. These mice die shortly after birth showing various abnormalities particularly in the lung, heart and limb, directly related to BM defects. However, despite the fact that both nidogens are found in all BMs, some BMs in these mice appeared ultrastructurally normal. Mice lacking the high affinity binding site on the laminin g1 chain that is present in most laminin isoforms showed strikingly different phenotypes. While changes in the lung are common, these mice do not display cardiac changes and show a highly penetrant renal aplasia not seen in nidogen double null mice. We were therefore interested to analyse the skin phenotype in these mice in comparison to the nidogen double null mice to understand the biological contribution of the laminin nidogen interactions for nidogen function in skin development. Detailed analysis of the skin BMs revealed different phenotypes between the two mouse strains indicating differences in the role of nidogens and the laminin nidogen interaction for skin physiology