Lysyl Oxidase Is Required for Vascular and Diaphragmatic Development in Mice*

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 over-lapping 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 insta-bility with ruptured arterial aneurysms and diaphrag-matic rupture. Microscopic analysis of the aorta demon-strated fragmented elastic fiber architecture in homozygous mutant null mice. LOX activity, as assesse