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First published online 3 March 2004
doi: 10.1242/dev.01037

Development 131, 1619-1628 (2004)
Published by The Company of Biologists 2004
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Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development

Ernst Pöschl1,*, Ursula Schlötzer-Schrehardt2, Bent Brachvogel1, Kenji Saito1,3, Yoshifumi Ninomiya3 and Ulrike Mayer4

1 Department of Experimental Medicine I, University Erlangen-Nürnberg, 91054 Erlangen, Germany
2 Department of Ophthalmology, University Erlangen-Nürnberg, 91054 Erlangen, Germany
3 Department of Molecular Biology and Biochemistry, Okayama University Medical School, Okayama 700, Japan
4 Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK

* Author for correspondence (e-mail: epoeschl{at}molmed.uni-erlangen.de)

Accepted 12 December 2003

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 {alpha}1(IV)2{alpha}2(IV) for basement membrane assembly and embryonic development, we generated a null allele of the Col4a1/2 locus in mice, thereby ablating both {alpha}-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.

Key words: Collagen IV, Col4a1, Col4a2, Knockout, Basement membrane, Development






© The Company of Biologists Ltd 2004