Perinatal Lethal Osteogenesis Imperfecta in Transgenic Mice Bearing an Engineered Mutant Pro-alpha 1(I) Collagen Gene

Substitutions of single glycine residues of alpha 1(I) collagen have previously been associated with the inherited disease osteogenesis imperfecta type II. Transgenic mice bearing a mutant alpha 1(I) collagen gene into which specific glycine substitutions have been engineered show a dominant lethal phenotype characteristic of the human disease, and demonstrate that as little as 10% mutant gene expression can disrupt normal collagen function.