severe osteogenesis imperfecta in cyclophilin b–deficient mice还有严重的成骨不全症小鼠杂交.pdfVIP

Severe Osteogenesis Imperfecta in Cyclophilin B–Deficient Mice 1 2 3 4 5 Jae Won Choi , Shari L. Sutor , Lonn Lindquist , Glenda L. Evans , Benjamin J. Madden , H. Robert 5 4 4 1,3 Bergen, III , Theresa E. Hefferan , Michael J. Yaszemski , Richard J. Bram * 1 Department of Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America, 2 Department of Transplant Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America, 3 Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America, 4 Department of Orthopedics Research, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America, 5 Mayo Proteomics Research Center, Mayo Clinic College of Medicine, Rochester, Minnesota, United States of America Abstract Osteogenesis Imperfecta (OI) is a human syndrome characterized by exquisitely fragile bones due to osteoporosis. The majority of autosomal dominant OI cases result from point or splice site mutations in the type I collagen genes, which are thought to lead to aberrant osteoid within developing bones. OI also occurs in humans with homozygous mutations in Prolyl-3-Hydroxylase-1 (LEPRE1). Although P3H1 is known to hydroxylate a single residue (pro-986) in type I collagen chains, it is unclear how this modification acts to facilitate collagen fibril formation. P3H1 exists in a complex with CRTAP and the peptidyl-prolyl isomerase cyclophilin B (CypB), encoded by the Ppib gene. Mutations in CRTAP cause OI in mice and humans, through an unknown mechanism, while the role of