Lysyl oxidase is required for vascular and diaphragmatic development in mice

Ian K. Hornstra, Shonyale Birge, Barry Starcher, Allen J. Bailey, Robert P. Mecham, Steven D. Shapiro

Research output: Contribution to journalArticlepeer-review

228 Scopus citations

Abstract

Lysyl oxidase (LOX) is an enzyme responsible for the cross-linking of collagen and elastin both in vitro and in vivo. The unique functions of the individual members of this multigene family have been difficult to ascertain because of highly conserved catalytic domains and overlapping tissue expression patterns. To address this problem of functional and structural redundancy and to determine the role of LOX in the development of tissue integrity, Lox gene expression was deleted by targeted mutagenesis in mice. Lox-targeted mice (LOX-/-) died soon after parturition, exhibiting cardiovascular instability with ruptured arterial aneurysms and diaphragmatic rupture. Microscopic analysis of the aorta demonstrated fragmented elastic fiber architecture in homozygous mutant null mice. LOX activity, as assessed by desmosine (elastin cross-link) analysis, was reduced by ∼60% in the aorta and lungs of homozygous mutant animals compared with wild type mice. Immature collagen cross-links were decreased but to a lesser degree than elastin cross-links in LOX-/- mice. Thus, lysyl oxidase appears critical during embryogenesis for structural stability of the aorta and diaphragm and connective tissue development.

Original languageEnglish
Pages (from-to)14387-14393
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number16
DOIs
StatePublished - Apr 18 2003

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