Evidence of nidogen-2 compensation for nidogen-1 deficiency in transgenic mice.
Previous studies have shown that inhibition of nidogen-laminin binding interferes with basement membrane stabilization in various mouse organ cultures while no overt phenotype has been observed following inactivation of the nidogen-1 gene in mice. We have now used recombinant mouse nidogen-1 and nidogen-2 in order to evaluate a possible compensation between the two isoforms in the knock-out mice. Essentially, a comparable in vitro binding of nidogens-1 and -2 to the same laminin gamma1 chain structure and to several other basement membrane proteins has been revealed. Quantitative radioimmuno-assays have demonstrated high concentrations of nidogen-1 exceeding those of laminin gamma1 and nidogen-2 by factors of 5 and 20-50, respectively, in tissue extracts of wild-type mice. A three- to sevenfold increase in nidogen-2 was observed in heart and muscle of mice with nidogen-1 deficiency and confirmed by a similar increase in the intensity of immunogold staining of these tissues. However, a few of the tissues from mice with the gene knock-out still contained some nidogen-1-like immunoreactivity (1% of wild-type). Furthermore, both nidogen isoforms showed a similar distribution in various organs during embryonic development which, however, as shown previously, changed in some adult tissues. The data support the nidogen-2 compensation hypothesis to explain the limited phenotype observed following elimination of the nidogen-1 gene.
Miosge
Nicolai
N
Department of Histology, Georg-August-Universität Göttingen, D-37075, Göttingen, Germany. nmiosge@gwdg.de
Sasaki
Takako
T
Timpl
Rupert
R
D000222:Adaptation, Physiological; D000818:Animals; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000502:physiology*; D015815:Cell Adhesion Molecules; D004622:Embryo, Mammalian / Q000378:metabolism; D005314:Embryonic and Fetal Development; D007158:Immunologic Techniques; D007797:Laminin / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000502:physiology*; D051379:Mice / Q000196:embryology; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010641:Phenotype; D011994:Recombinant Proteins / Q000378:metabolism; D015854:Up-Regulation
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D007797:Laminin; D008024:Ligands; D008562:Membrane Glycoproteins; C114729:NID2 protein, human; D011994:Recombinant Proteins; C089141:laminin gamma 1; C029967:nidogen