scholarly journals Characterization of three osteogenesis imperfecta collagen α 1(I) glycine to serine mutations demonstrating a position-dependent gradient of phenotypic severity

1992 ◽  
Vol 288 (1) ◽  
pp. 131-135 ◽  
Author(s):  
J F Bateman ◽  
I Moeller ◽  
M Hannagan ◽  
D Chan ◽  
W G Cole
Keyword(s):  
Osteogenesis Imperfecta ◽  
Triple Helix ◽  
Type I Collagen ◽  
Type I ◽  
Disruptive Effect ◽  
Collagen Triple Helix ◽  
C Terminus ◽  
Glycine Substitution ◽  
C And N

Type I collagen alpha 1(I) glycine to serine substitutions, resulting from G-to-A mutations, were defined in three cases of osteogenesis imperfecta (OI). The Gly substitutions displayed a gradient of phenotypic severity according to the location of the mutation in the collagen triple helix. The most C-terminal of these, Gly565 to Ser, led to the lethal perinatal (type II) form of OI, whereas the more N-terminal mutations, Gly415 and Gly352 to Ser, led to severe OI (type III/IV) and moderate OI (type IVB) respectively. These data support the notion that glycine substitutions towards the C-terminus of the alpha 1(I) or alpha 2(I) chains will be more clinically severe than those towards the N-terminus. This results from the more disruptive effect of the mutations at the C-terminus on helix initiation and C- and N-terminal helix directional propagation. This generalization must be modified by considering the nature of the glycine substitution and the surrounding amino acid sequence, since the helix is composed of subdomains of differing stability which will affect the ability of helix re-nucleation and propagation.

scholarly journals Structural Heterogeneity of Type I Collagen Triple Helix and Its Role in Osteogenesis Imperfecta

2007 ◽  
Vol 283 (8) ◽  
pp. 4787-4798 ◽  
Author(s):  
Elena Makareeva ◽  
Edward L. Mertz ◽  
Natalia V. Kuznetsova ◽  
Mary B. Sutter ◽  
Angela M. DeRidder ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Triple Helix ◽  
Type I Collagen ◽  
Structural Heterogeneity ◽  
Type I ◽  
Collagen Triple Helix

A Cysteine for Glycine Substitution at Position 175 in an α1 (I) Chain of Type I Collagen Produces A Clinically Heterogeneous Form of Osteogenesis Imperfecta

1993 ◽  
Vol 29 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Mary K. Wirtz ◽  
Velidi H. Rao ◽  
Robert W. Glanville ◽  
Michael E. Labhard ◽  
Petrus J. Pretorius ◽  
...  
Keyword(s):  
Osteogenesis Imperfecta ◽  
Type I Collagen ◽  
Type I ◽  
Glycine Substitution

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 Hearing Loss in Osteogenesis Imperfecta: Characteristics and Treatment Considerations

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Joseph P. Pillion ◽  
David Vernick ◽  
Jay Shapiro
Keyword(s):  
Hearing Loss ◽  
Osteogenesis Imperfecta ◽  
Hearing Aids ◽  
Type I Collagen ◽  
Treatment Options ◽  
Type I ◽  
Collagen Triple Helix ◽  
Treatment Considerations ◽  
Heritable Disorder ◽  
Blue Sclerae

Osteogenesis imperfecta (OI) is the most common heritable disorder of connective tissue. It is associated with fractures following relatively minor injury, blue sclerae, dentinogenesis imperfecta, increased joint mobility, short stature, and hearing loss. Structures in the otic capsule and inner ear share in the histologic features common to other skeletal tissues. OI is due to mutations involving several genes, the most commonly involved are the COL1A1 or COL1A2 genes which are responsible for the synthesis of the proalpha-1 and proalpha-2 polypeptide chains that form the type I collagen triple helix. A genotype/phenotype relationship to hearing loss has not been established in OI. Hearing loss is commonly found in OI with prevalence rates ranging from 50 to 92% in some studies. Hearing loss in OI may be conductive, mixed, or sensorineural and is more common by the second or third decade. Treatment options such as hearing aids, stapes surgery, and cochlear implants are discussed.

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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