Specific ablation of the nidogen-binding site in the laminin gamma1 chain interferes with kidney and lung development.
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, gamma1III4, 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.
Willem
Michael
M
Max-Planck-Institute for Biochemistry, Department of Protein Chemistry, 82152 Martinsried, Germany.
Miosge
Nicolai
N
Halfter
Willi
W
Smyth
Neil
N
Jannetti
Iris
I
Burghart
Elke
E
Timpl
Rupert
R
Mayer
Ulrike
U
D000818:Animals; D001665:Binding Sites; D002678:Chimera; D016326:Extracellular Matrix Proteins; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000196:embryology* / Q000648:ultrastructure; D007797:Laminin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008168:Lung / Q000196:embryology* / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000502:physiology; D014162:Transfection
D016326:Extracellular Matrix Proteins; D007797:Laminin; D008562:Membrane Glycoproteins; C089141:laminin gamma 1; C029967:nidogen