The Absence of Nidogen 1 Does Not Affect Murine Basement Membrane Formation

Abstract

Nidogen 1 is a highly conserved protein in mammals,Drosophila melanogaster, Caenorhabditis elegans, and ascidians and is found in all basement membranes. It has been proposed that nidogen 1 connects the laminin and collagen IV networks, so stabilizing the basement membrane, and integrates other proteins, including perlecan, into the basement membrane. To define the role of nidogen 1 in basement membranes in vivo, we produced a null mutation of the NID-1 gene in embryonic stem cells and used these to derive mouse lines. Homozygous animals produce neither nidogen 1 mRNA nor protein. Surprisingly, they show no overt abnormalities and are fertile, their basement membrane structures appearing normal. Nidogen 2 staining is increased in certain basement membranes, where it is normally only found in scant amounts. This occurs by either redistribution from other extracellular matrices or unmasking of nidogen 2 epitopes, as its production does not appear to be upregulated. The results show that nidogen 1 is not required for basement membrane formation or maintenance.

ACKNOWLEDGMENTS

This work was supported by a grant from the German Research Foundation (FOR 265/2) and by the Bundesministerium für Bildung, Wissenschaft, Forschung, und Technologie (grant ZMMK-TV25).

We thank Christian Frie and Petra Weskamp (Institute for Biochemistry II) and Marion Reibetanz (Department of Dermatology) for excellent technical assistance. We are greatly indebted to R. Timpl and U. Mayer (Max Planck Institute for Biochemistry, Martinsried, Germany) for access to reagents and W. Müller (Institute for Genetics, University of Cologne) for helpful discussions.

M.M. and N.S. contributed equally to this work.