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Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development

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Pöschl, Ernst, Schlötzer-Schrehardt, Ursula, Brachvogel, Bent, Saito, Kenji, Ninomiya, Yoshifumi, Mayer, Ulrike·2004·Development
DOI 10.1242/dev.01037
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Abstract

Basement membranes are specialized extracellular matrices consisting of tissue-specific organizations of multiple matrix molecules and serve as structural barriers as well as substrates for cellular interactions. The network of collagen IV is thought to define the scaffold integrating other components such as, laminins, nidogens or perlecan, into highly organized supramolecular architectures. To analyze the functional roles of the major collagen IV isoform α1(IV)2α2(IV) for basement membrane assembly and embryonic development, we generated a null allele of the Col4a1/2 locus in mice, thereby ablating both α-chains. Unexpectedly, embryos developed up to E9.5 at the expected Mendelian ratio and showed a variable degree of growth retardation. Basement membrane proteins were deposited and assembled at expected sites in mutant embryos, indicating that this isoform is dispensable for matrix deposition and assembly during early development. However, lethality occurred between E10.5-E11.5, because of structural deficiencies in the basement membranes and finally by failure of the integrity of Reichert's membrane. These data demonstrate for the first time that collagen IV is fundamental for the maintenance of integrity and function of basement membranes under conditions of increasing mechanical demands, but dispensable for deposition and initial assembly of components. Taken together with other basement membrane protein knockouts, these data suggest that laminin is sufficient for basement membrane-like matrices during early development, but at later stages the specific composition of components including collagen IV defines integrity, stability and functionality.

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Metadata

Authors
Pöschl, E., Schlötzer-Schrehardt, U., Brachvogel, B., Saito, K., Ninomiya, Y., & Mayer, U.
Venue
Development
Publisher
The Company of Biologists
Published
2004-04-01
Volume
131
Issue
7
Pages
1619-1628
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
DOI
10.1242/dev.01037
OpenAlex
W2143156113
Cited by
816
References
0
FWCI
13.86
Type
journal article
Language
en
Open access
bronze

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