scholarly journals Effects of tissue hydration on nanoscale structural morphology and mechanics of individual Type I collagen fibrils in the Brtl mouse model of Osteogenesis Imperfecta

2012 ◽  
Vol 180 (3) ◽  
pp. 428-438 ◽  
Author(s):  
Arika D. Kemp ◽  
Chad C. Harding ◽  
Wayne A. Cabral ◽  
Joan C. Marini ◽  
Joseph M. Wallace
Keyword(s):  
Mouse Model ◽  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Collagen Fibrils ◽  
Type I ◽  
Structural Morphology ◽  
Tissue Hydration ◽  
Individual Type

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

Effects of Hydration on Nanoscale Structural Morphology and Mechanics of Individual Type I Collagen Fibrils

2012 ◽  
Vol 1465 ◽  
Author(s):  
Joseph M. Wallace ◽  
Chad Harding ◽  
Arika Kemp
Keyword(s):  
Type I Collagen ◽  
Type I ◽  
Mechanical Function ◽  
Structural Morphology ◽  
Force Microscopy ◽  
Atomic Force ◽  
Individual Type ◽  
Nanoscale Structure ◽  
Tail Tendon ◽  
Morphology And Mechanical Properties

ABSTRACTType I collagen is one of the most vital proteins in our bodies and serves a number of structural roles. Despite collagen’s importance, little is known about its nanoscale morphology in tissues and how morphology relates to mechanical function. This study directly probes nanoscale structure and mechanics in collagen as a function of hydration utilizing atomic force microscopy investigations of the mouse tail tendon. We demonstrate that collagen morphology and mechanical properties at the nanoscale change with dehydration, indicating that hydration is a factor which must be considered when performing studies at any length scale in collagen-based tissues. Studies are underway to further investigate this phenomenon and to determine how these properties change with disease in tendon and other Type I collagen-based tissues.

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.

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 Substitutions of aspartic acid for glycine-220 and of arginine for glycine-664 in the triple helix of the pro α1(I) chain of type I procollagen produce lethal osteogenesis imperfecta and disrupt the ability of collagen fibrils to incorporate crystalline hydroxyapatite

1995 ◽  
Vol 311 (3) ◽  
pp. 815-820 ◽  
Author(s):  
A A Culbert ◽  
M P Lowe ◽  
M Atkinson ◽  
P H Byers ◽  
G A Wallis ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Aspartic Acid ◽  
Triple Helix ◽  
Type I Collagen ◽  
Collagen Fibrils ◽  
Morphological Data ◽  
Type I ◽  
Type Ii ◽  
Col1a1 Gene ◽  
Type I Procollagen

We identified two infants with lethal (type II) osteogenesis imperfecta (OI) who were heterozygous for mutations in the COL1A1 gene that resulted in substitutions of aspartic acid for glycine at position 220 and arginine for glycine at position 664 in the product of one COL1A1 allele in each individual. In normal age- and site-matched bone, approximately 70% (by number) of the collagen fibrils were encrusted with plate-like crystallites of hydroxyapatite. In contrast, approximately 5% (by number) of the collagen fibrils in the probands' bone contained crystallites. In contrast with normal bone, the c-axes of hydroxyapatite crystallites were sometimes poorly aligned with the long axis of fibrils obtained from OI bone. Chemical analysis showed that the OI samples contained normal amounts of calcium. The probands' bone samples contained type I collagen, overmodified type I collagen and elevated levels of type III and V collagens. On the basis of biochemical and morphological data, the fibrils in the OI samples were co-polymers of normal and mutant collagen. The results are consistent with a model of fibril mineralization in which the presence of abnormal type I collagen prevents normal collagen in the same fibril from incorporating hydroxyapatite crystallites.

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