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Altered collagen structure in mouse tail tendon lacking the alpha 2(I) chain
D J McBride1, V Choe, J R Shapiro
1Division of Geriatric Medicine and Gerontology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Journal of Molecular Biology
|July 11, 1997
Summary
The absence of alpha 2(I) chains in type I collagen disrupts molecular packing, affecting fibril organization and leading to reduced mechanical strength in tissues like tendons and bone. This impacts overall body size and bone integrity.
Area of Science:
- Biochemistry
- Structural Biology
- Biophysics
Background:
- Type I collagen, crucial for connective tissues, typically consists of two alpha 1(I) chains and one alpha 2(I) chain.
- The functional significance of this heterotrimeric structure remains largely unelucidated.
- The oim mouse model offers a unique system to study the consequences of alpha 2(I) chain loss on collagen structure and function.
Purpose of the Study:
- To investigate the structural and functional impact of alpha 2(I) chain deficiency in type I collagen.
- To explore how the loss of alpha 2(I) chains affects collagen fibril organization and mechanical properties.
- To understand the role of collagen chain non-equivalence in tissue development and integrity.
Main Methods:
- X-ray diffraction analysis of tail tendons from oim/oim (complete alpha 2(I) loss) and oim/+ (partial alpha 2(I) loss) mice compared to controls.
- Assessment of enzymatic susceptibility of collagen.
- Phenotypic analysis of body size and tendon bundle dimensions.
Main Results:
- Complete absence of alpha 2(I) chains in oim/oim mice led to decreased axial packing order and loss of crystalline lateral packing in tail tendons.
- Heterozygous oim/+ mice exhibited co-polymeric fibrils of homotrimeric and heterotrimeric collagen, hindering crystalline lateral packing.
- Alpha 2(I) chain absence increased enzymatic susceptibility at a specific site and resulted in reduced body size and smaller tendon bundles.
Conclusions:
- The non-equivalence of collagen chains (alpha 1(I) vs. alpha 2(I)) is critical for lateral molecular interactions and long-range axial order in type I collagen fibrils.
- Disruption of molecular packing due to alpha 2(I) chain loss impacts tissue-level organization and mechanical properties.
- These molecular and fibrillar alterations likely contribute to the osteopenia and reduced bone strength observed in oim mice, mirroring human osteogenesis imperfecta.