title: Gene structure and functional analysis of the mouse nidogen-2 gene: nidogen-2 is not essential for basement membrane formation in mice.
abstract: 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.
authors.affiliation: Department of Protein Chemistry, Max-Planck-Institute for Biochemistry, D-82152 Martinsried, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schymeinsky
authors.forename: Sabine
authors.initials: S
authors.lastname: Nedbal
authors.forename: Nicolai
authors.initials: N
authors.lastname: Miosge
authors.forename: Ernst
authors.initials: E
authors.lastname: Pöschl
authors.forename: Cherie
authors.initials: C
authors.lastname: Rao
authors.forename: David R
authors.initials: DR
authors.lastname: Beier
authors.forename: William C
authors.initials: WC
authors.lastname: Skarnes
authors.forename: Rupert
authors.initials: R
authors.lastname: Timpl
authors.forename: Bernhard L
authors.initials: BL
authors.lastname: Bader
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism* / Q000648:ultrastructure; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D003001:Cloning, Molecular; D024141:Collagen Type IV / Q000096:biosynthesis; D005091:Exons; D005328:Fetal Viability; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis; D006720:Homozygote; D007438:Introns; D007797:Laminin / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000032:analysis / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010641:Phenotype; D020161:Physical Chromosome Mapping; D011863:Radioimmunoassay
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D024141:Collagen Type IV; D019812:Heparan Sulfate Proteoglycans; D007797:Laminin; D008562:Membrane Glycoproteins; C114729:NID2 protein, human; C089141:laminin gamma 1; C029967:nidogen; C071927:perlecan