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Molecular and Cellular Biology, October 2002, p. 6820-6830, Vol. 22, No. 19
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.19.6820-6830.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Gene Structure and Functional Analysis of the Mouse Nidogen-2 Gene: Nidogen-2 Is Not Essential for Basement Membrane Formation in Mice

Jürgen Schymeinsky,1 Sabine Nedbal,1 Nicolai Miosge,2 Ernst Pöschl,3 Cherie Rao,4 David R. Beier,4 William C. Skarnes,5 Rupert Timpl,1 and Bernhard L. Bader1*

Department of Protein Chemistry, Max-Planck-Institute for Biochemistry, D-82152 Martinsried,1 Center of Anatomy, Department of Histology, University of Göttingen, D-37075 Göttingen,2 Department of Experimental Medicine I, University of Erlangen-Nürnberg, D-91045 Erlangen, Germany,3 Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115,4 Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 947205

Received 15 April 2002/ Returned for modification 28 May 2002/ Accepted 10 June 2002

Nidogens are highly conserved proteins in vertebrates and invertebrates and are found in almost all basement membranes. According to the classical hypothesis of basement membrane organization, nidogens connect the laminin and collagen IV networks, so stabilizing the basement membrane, and integrate other proteins. In mammals two nidogen proteins, nidogen-1 and nidogen-2, have been discovered. Nidogen-2 is typically enriched in endothelial basement membranes, whereas nidogen-1 shows broader localization in most basement membranes. Surprisingly, analysis of nidogen-1 gene knockout mice presented evidence that nidogen-1 is not essential for basement membrane formation and may be compensated for by nidogen-2. In order to assess the structure and in vivo function of the nidogen-2 gene in mice, we cloned the gene and determined its structure and chromosomal location. Next we analyzed mice carrying an insertional mutation in the nidogen-2 gene that was generated by the secretory gene trap approach. Our molecular and biochemical characterization identified the mutation as a phenotypic null allele. Nidogen-2-deficient mice show no overt abnormalities and are fertile, and basement membranes appear normal by ultrastructural analysis and immunostaining. Nidogen-2 deficiency does not lead to hemorrhages in mice as one may have expected. Our results show that nidogen-2 is not essential for basement membrane formation or maintenance.

* Corresponding author. Mailing address: Department of Molecular Biology, Max-Planck-Institute for Biochemistry, D-82152 Martinsried, Germany. Phone: 49-089-85783531. Fax: 49-089-85782452. E-mail: bbader{at}biochem.mpg.de.

Molecular and Cellular Biology, October 2002, p. 6820-6830, Vol. 22, No. 19
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.19.6820-6830.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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