After exclusion of type II perinatal lethal OI, a pathological evaluation of the cause of death in 82% of the more severe OI type III and 39% of milder OI type I and OI type IV was considered respiratory. Increasing scoliosis correlates with increasing restrictive lung disease. However, the authors of that study note that ����the presence of more severe restrictive lung disease with relatively smaller curve magnitudes in the population with OI indicates the possibility of intrinsic pulmonary abnormality����. In addition, there are isolated reports of L-Glutamine abnormal collagen in the lungs of individuals with severe OI. Therefore, these data combined with our results suggest that a primary lung defect in individuals with OI may be a consequence of abnormal collagen synthesis, in addition to secondary consequences of skeletal abnormalities. As with other connective tissue diseases, skin laxity and skin fragility have been observed in some individuals with OI, and it has long been known that cultured dermal fibroblasts from individuals with OI make abnormal proteins. Even if there is no obvious clinical skin abnormality, there can be alterations of the mechanical properties of the skin in OI, similar to that seen in the Crtap-/- mice. Furthermore, recently described mice that are null for the Ppib gene, which encodes CYPB, also demonstrate skin laxity as well as weakness, suggesting that loss of components of the prolyl 3-hydroxylation complex may lead to common skin findings. In addition, sections of the dermis of mice that are heterozygous for a null allele of Col1a1 appear strikingly similar to the Crtap-/- skin sections. These findings suggest that abnormal skin, albeit subclinical in most cases, may be a part of the phenotype of both classical OI and OI caused by mutations in CRTAP or LEPRE1. In summary, absence of CRTAP in the mouse results in the pathophysiology of multiple organ systems, and CRTAP is required at the molecular level for proper prolyl Mebhydrolin napadisylate 3-hydroxyation of several types of fibrillar collagen and for the expression of the P3H1 protein in humans.