Embryonic mesodermal defects in α5 integrin-deficient mice

Abstract

A loss of function mutation of the murineα5 integrin gene generated by gene targeting in embryonic stem cells is a recessive embryonic lethal. The mutant embryos start to show observable defects by day 9 of gestation and die around day 10-11. Theα5-null embryos have pronounced defects in posterior trunk and yolk sac mesodermal structures, suggesting a role forα5 β1 integrin in mesoderm formation, movement or function. However, the embryos progress significantly further than embryos null for fibronectin, for whichα5 β1 integrin is a receptor, suggesting the involvement of other fibronectin receptors. In vitro studies on cells derived from theα5-null embryos confirm that theα5 β1 integrin is not expressed on mutant cells and show that the mutant cells are able to assemble fibronectin matrix, form focal contacts, and migrate on fibronectin despite the complete absence of theα5 β1 fibronectin receptor integrin. All these functions have previously been thought to involve or requireα5 β1. The results presented show that these cellular functions involving fibronectin can proceed using other receptors.