このエントリーをはてなブックマークに追加
ID 32985
フルテキストURL
著者
Pöschl, Ernst Department of Experimental Medicine I, University Erlangen-Nürnberg
Schlötzer-Schrehardt, Ursula Department of Ophthalmology, University Erlangen-Nürnberg
Brachvogel, Bent Department of Experimental Medicine I, University Erlangen-Nürnberg
Saito, Kenji Department of Molecular Biology and Biochemistry, Okayama University Medical School
Ninomiya, Yoshifumi Department of Molecular Biology and Biochemistry, Okayama University Medical School
Mayer, Ulrike Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester
抄録
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.
キーワード
Collagen IV
Col4a1
Col4a2
Knockout
Basement
membrane
Development
備考
Digital Object Identifer:10.1242/dev.01037
Published with permission from the copyright holder. This is the institute's copy, as published in Development, April 2004, Volume 131, Issue 7, Pages 1619-1628.
Publisher URL:http://dx.doi.org/10.1242/dev.01037
Copyright 2004 © The Company of Biologists Ltd. All rights reserved.
発行日
2004-04
出版物タイトル
Development
131巻
7号
出版者
The Company of Biologists
開始ページ
1619
終了ページ
1628
ISSN
0950-1991
NCID
AA10667805
資料タイプ
学術雑誌論文
言語
English
著作権者
The Company of Biologists
論文のバージョン
publisher
査読
有り
DOI
PubMed ID
Web of Sience KeyUT
Submission Path
biology_general/3