In close concert with projects 1 and 2, we seek common molecular features of abnormal bone collagen expression in tissue from mice and human cases of osteogenesis imperfecta (01) caused by mutations in genes encoding the CRTAP/P3H1/CYPB and FKBP10/HSP47 complexes and newly identified genes causing recessive 01. The significance and inter-relationships of defective prolyl 3-hydroxylation, associated post-translational over modification of lysine residues and abnormal cross-linking are the focus and basis of hypothesis-driven studies. One goal is to thoroughly test the possibility that abnormal post-translational chemistry, and in particular cross-linking, underlies the brittle bone phenotype. Though the focus is novel recessive forms of 01, the significance of the findings is likely to extend across all forms of 01.
The specific aims are directed at establishing the cross-linking phenotype of bone collagen from mouse models and available human 01 cases, seeking a common pathology and common underlying mechanism.
|Machol, Keren; Jain, Mahim; Almannai, Mohammed et al. (2016) Corner fracture type spondylometaphyseal dysplasia: Overlap with type II collagenopathies. Am J Med Genet A :|
|Grafe, Ingo; Alexander, Stefanie; Yang, Tao et al. (2016) Sclerostin Antibody Treatment Improves the Bone Phenotype of Crtap(-/-) Mice, a Model of Recessive Osteogenesis Imperfecta. J Bone Miner Res 31:1030-40|
|Rajagopal, Abbhirami; Homan, Erica P; Joeng, Kyu Sang et al. (2016) Restoration of the serum level of SERPINF1 does not correct the bone phenotype in Serpinf1 null mice. Mol Genet Metab 117:378-82|
|Lindert, Uschi; Cabral, Wayne A; Ausavarat, Surasawadee et al. (2016) MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta. Nat Commun 7:11920|
|Hosseininia, S; Weis, M A; Rai, J et al. (2016) Evidence for enhanced collagen type III deposition focally in the territorial matrix of osteoarthritic hip articular cartilage. Osteoarthritis Cartilage 24:1029-35|
|Heard, Melissa E; Besio, Roberta; Weis, MaryAnn et al. (2016) Sc65-Null Mice Provide Evidence for a Novel Endoplasmic Reticulum Complex Regulating Collagen Lysyl Hydroxylation. PLoS Genet 12:e1006002|
|Lietman, Caressa D; Marom, Ronit; Munivez, Elda et al. (2015) A transgenic mouse model of OI type V supports a neomorphic mechanism of the IFITM5 mutation. J Bone Miner Res 30:489-98|
|Patel, R M; Nagamani, S C S; Cuthbertson, D et al. (2015) A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers. Clin Genet 87:133-40|
|Lu, Linchao; Harutyunyan, Karine; Jin, Weidong et al. (2015) RECQL4 Regulates p53 Function In Vivo During Skeletogenesis. J Bone Miner Res 30:1077-89|
|Posey, Jennifer E; Burrage, Lindsay C; Campeau, Philippe M et al. (2015) Adult presentation of X-linked Conradi-HÃ¼nermann-Happle syndrome. Am J Med Genet A 167:1309-14|
Showing the most recent 10 out of 66 publications