Abnormal type I collagen glycosylation pattern and cross-linking in a cyclophilin B KO mouse model of recessive osteogenesis imperfecta

2013 ◽  
Author(s):  
Wayne Cabral ◽  
Irina Perdivara ◽  
MaryAnn Weis ◽  
Masahiko Terajima ◽  
Angela Blissett ◽  
...  
Keyword(s):  
Mouse Model ◽  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Cross Linking ◽  
Type I ◽  
Glycosylation Pattern ◽  
Cyclophilin B

scholarly journals Abnormal Type I Collagen Post-translational Modification and Crosslinking in a Cyclophilin B KO Mouse Model of Recessive Osteogenesis Imperfecta

PLoS Genetics ◽  
2014 ◽  
Vol 10 (6) ◽  
pp. e1004465 ◽  
Author(s):  
Wayne A. Cabral ◽  
Irina Perdivara ◽  
MaryAnn Weis ◽  
Masahiko Terajima ◽  
Angela R. Blissett ◽  
...  
Keyword(s):  
Mouse Model ◽  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Type I ◽  
Post Translational Modification ◽  
Cyclophilin B

Abnormal type I collagen folding and matrix deposition in a cyclophilin B KO mouse model of recessive osteogenesis imperfecta

Bone ◽  
2012 ◽  
Vol 50 ◽  
pp. S38
Author(s):  
W.A. Cabral⁎ ◽  
A.M. Barnes ◽  
E. Makareeva ◽  
M. Weis ◽  
W. Chang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Type I ◽  
Cyclophilin B ◽  
Matrix Deposition

scholarly journals Cyclophilin-B Modulates Collagen Cross-linking by Differentially Affecting Lysine Hydroxylation in the Helical and Telopeptidyl Domains of Tendon Type I Collagen

2016 ◽  
Vol 291 (18) ◽  
pp. 9501-9512 ◽  
Author(s):  
Masahiko Terajima ◽  
Yuki Taga ◽  
Yulong Chen ◽  
Wayne A. Cabral ◽  
Guo Hou-Fu ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Cross Linking ◽  
Type I ◽  
Cyclophilin B ◽  
Lysine Hydroxylation ◽  
Collagen Cross Linking

scholarly journals Respiratory defects in the CrtapKO mouse model of osteogenesis imperfecta

2020 ◽  
Vol 318 (4) ◽  
pp. L592-L605
Author(s):  
Milena Dimori ◽  
Melissa E. Heard-Lipsmeyer ◽  
Stephanie D. Byrum ◽  
Samuel G. Mackintosh ◽  
Richard C. Kurten ◽  
...  
Keyword(s):  
Mouse Model ◽  
Osteogenesis Imperfecta ◽  
Respiratory System ◽  
Type I Collagen ◽  
Lung Parenchyma ◽  
Lung Fibroblasts ◽  
Whole Body ◽  
Type I ◽  
Forced Oscillation Technique ◽  
Expiratory Time

Respiratory disease is a leading cause of mortality in patients with osteogenesis imperfecta (OI), a connective tissue disease that causes severely reduced bone mass and is most commonly caused by dominant mutations in type I collagen genes. Previous studies proposed that impaired respiratory function in OI patients was secondary to skeletal deformities; however, recent evidence suggests the existence of a primary lung defect. Here, we analyzed the lung phenotype of Crtap knockout (KO) mice, a mouse model of recessive OI. While we confirm changes in the lung parenchyma that are reminiscent of emphysema, we show that CrtapKO lung fibroblasts synthesize type I collagen with altered posttranslation modifications consistent with those observed in bone and skin. Unrestrained whole body plethysmography showed a significant decrease in expiratory time, resulting in an increased ratio of inspiratory time over expiratory time and a concomitant increase of the inspiratory duty cycle in CrtapKO compared with WT mice. Closed-chest measurements using the forced oscillation technique showed increased respiratory system elastance, decreased respiratory system compliance, and increased tissue damping and elasticity in CrtapKO mice compared with WT. Pressure-volume curves showed significant differences in lung volumes and in the shape of the curves between CrtapKO mice and WT mice, with and without adjustment for body weight. This is the first evidence that collagen defects in OI cause primary changes in lung parenchyma and several respiratory parameters and thus negatively impact lung function.

scholarly journals Morphological and mechanical characterization of bone phenotypes in the Amish G610C murine model of osteogenesis imperfecta

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255315
Author(s):  
Rachel Kohler ◽  
Carli A. Tastad ◽  
Amy Creecy ◽  
Joseph M. Wallace
Keyword(s):  
Mouse Model ◽  
Osteogenesis Imperfecta ◽  
Intervention Studies ◽  
Type I Collagen ◽  
Type I ◽  
Micro Computed Tomography ◽  
Mineral Density ◽  
Collagen Formation ◽  
Genotype 2

Osteogenesis imperfecta (OI) is a hereditary bone disease where gene mutations affect Type I collagen formation resulting in osteopenia and increased fracture risk. There are several established mouse models of OI, but some are severe and result in spontaneous fractures or early animal death. The Amish Col1a2G610C/+ (G610C) mouse model is a newer, moderate OI model that is currently being used in a variety of intervention studies, with differing background strains, sexes, ages, and bone endpoints. This study is a comprehensive mechanical and architectural characterization of bone in G610C mice bred on a C57BL/6 inbred strain and will provide a baseline for future treatment studies. Male and female wild-type (WT) and G610C mice were euthanized at 10 and 16 weeks (n = 13–16). Harvested tibiae, femora, and L4 vertebrae were scanned via micro-computed tomography and analyzed for cortical and trabecular architectural properties. Femora and tibiae were then mechanically tested to failure. G610C mice had less bone but more highly mineralized cortical and trabecular tissue than their sex- and age-matched WT counterparts, with cortical cross-sectional area, thickness, and mineral density, and trabecular bone volume, mineral density, spacing, and number all differing significantly as a function of genotype (2 Way ANOVA with main effects of sex and genotype at each age). In addition, mechanical yield force, ultimate force, displacement, strain, and toughness were all significantly lower in G610C vs. WT, highlighting a brittle phenotype. This characterization demonstrates that despite being a moderate OI model, the Amish G610C mouse model maintains a distinctly brittle phenotype and is well-suited for use in future intervention studies.

scholarly journals Nanoscale morphology of Type I collagen is altered in the Brtl mouse model of Osteogenesis Imperfecta

2011 ◽  
Vol 173 (1) ◽  
pp. 146-152 ◽  
Author(s):  
Joseph M. Wallace ◽  
Bradford G. Orr ◽  
Joan C. Marini ◽  
Mark M. Banaszak Holl
Keyword(s):  
Mouse Model ◽  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Type I ◽  
Nanoscale Morphology

scholarly journals Restoration of Osteogenesis by CRISPR/Cas9 Genome Editing of the Mutated COL1A1 Gene in Osteogenesis Imperfecta

2021 ◽  
Vol 10 (14) ◽  
pp. 3141
Author(s):  
Hyerin Jung ◽  
Yeri Alice Rim ◽  
Narae Park ◽  
Yoojun Nam ◽  
Ji Hyeon Ju
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Disease Modeling ◽  
Bone Fragility ◽  
Osteogenic Potential ◽  
Type I ◽  
Gene Correction ◽  
Col1a1 Gene ◽  
Collagen Formation

Osteogenesis imperfecta (OI) is a genetic disease characterized by bone fragility and repeated fractures. The bone fragility associated with OI is caused by a defect in collagen formation due to mutation of COL1A1 or COL1A2. Current strategies for treating OI are not curative. In this study, we generated induced pluripotent stem cells (iPSCs) from OI patient-derived blood cells harboring a mutation in the COL1A1 gene. Osteoblast (OB) differentiated from OI-iPSCs showed abnormally decreased levels of type I collagen and osteogenic differentiation ability. Gene correction of the COL1A1 gene using CRISPR/Cas9 recovered the decreased type I collagen expression in OBs differentiated from OI-iPSCs. The osteogenic potential of OI-iPSCs was also recovered by the gene correction. This study suggests a new possibility of treatment and in vitro disease modeling using patient-derived iPSCs and gene editing with CRISPR/Cas9.

scholarly journals Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach

2021 ◽  
Vol 22 (1) ◽  
pp. 429
Author(s):  
Luca Bini ◽  
Domitille Schvartz ◽  
Chiara Carnemolla ◽  
Roberta Besio ◽  
Nadia Garibaldi ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Type I ◽  
Tandem Mass ◽  
Type Ii ◽  
Type Iii ◽  
Bioinformatic Tools ◽  
Proteomic Approach ◽  
Fibrillin 1 ◽  
Heritable Disorder

Osteogenesis imperfecta (OI) is a heritable disorder that mainly affects the skeleton. The inheritance is mostly autosomal dominant and associated to mutations in one of the two genes, COL1A1 and COL1A2, encoding for the type I collagen α chains. According to more than 1500 described mutation sites and to outcome spanning from very mild cases to perinatal-lethality, OI is characterized by a wide genotype/phenotype heterogeneity. In order to identify common affected molecular-pathways and disease biomarkers in OI probands with different mutations and lethal or surviving phenotypes, primary fibroblasts from dominant OI patients, carrying COL1A1 or COL1A2 defects, were investigated by applying a Tandem Mass Tag labeling-Liquid Chromatography-Tandem Mass Spectrometry (TMT LC-MS/MS) proteomics approach and bioinformatic tools for comparative protein-abundance profiling. While no difference in α1 or α2 abundance was detected among lethal (type II) and not-lethal (type III) OI patients, 17 proteins, with key effects on matrix structure and organization, cell signaling, and cell and tissue development and differentiation, were significantly different between type II and type III OI patients. Among them, some non–collagenous extracellular matrix (ECM) proteins (e.g., decorin and fibrillin-1) and proteins modulating cytoskeleton (e.g., nestin and palladin) directly correlate to the severity of the disease. Their defective presence may define proband-failure in balancing aberrances related to mutant collagen.

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