Altered collagen structure in mouse tail tendon lacking the alpha 2(I) chain
Altered collagen structure in mouse tail tendon lacking the alpha 2(I) chain
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DOI：
10.1006/jmbi.1997.1106
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发表时间：
1997-07-11
影响因子：
5.6
通讯作者：
Brodsky, B
中科院分区：
文献类型：
--
作者：
McBride, DJ;Choe, V;Brodsky, B
I型胶原蛋白是高等脊椎动物中胶原蛋白原纤维形成家族中最普遍的成员，其异源三聚体形式由两条α 1（I）链和一条α 2（I）多肽链组成。在I型胶原中具有两种不同链类型的功能重要性在很大程度上是不确定的。具有Cola-2基因突变（称为oim）的小鼠模型的存在导致非功能性pro α 2（I）链，这为探索由功能性α 2（I）链的完全（oim/oim小鼠）和部分（oim/+小鼠）损失引起的胶原结构变化提供了独特的机会。尾腱是一种具有明确的I型胶原分级组织的组织。对oim/oim与对照肌腱的X射线衍射研究表明，完全不存在α 2（I）链导致轴向堆积顺序减少和结晶横向堆积损失。这表明，三个链的非等效性是相邻分子之间的横向相互作用的一个重要决定因素，并可能参与在长距离轴向顺序在I型胶原蛋白的组织。在杂合子oim小鼠中发现了纯三聚体和异三聚体I型胶原分子，并且这些分子似乎存在于相同的共聚原纤维中，从而防止结晶横向堆积。除了在纤维水平上的这些变化之外，α 2（I）链的缺失导致在一个位点处的酶敏感性增加。观察到oim/oim小鼠具有减小的身体尺寸和较小的肌腱束，这可能是胶原蛋白中这些分子和纤维变化的结果。此外，骨原纤维中胶原分子堆积的类似改变可能导致具有oim突变的小鼠的骨质减少和骨强度降低，这也是人类成骨细胞的特征。(C)出版社：Academic Press Limited。
Type I collagen is the most prevalent member of the fibril forming family of collagens in higher vertebrates and its heterotrimeric form is comprised of two alpha 1(I) chains and one alpha 2(I) polypeptide chain. The functional importance of having two distinct chain types in type I collagen is largely undefined. The existence of a mouse model with a Cola-2 gene mutation (termed oim) that results in non-functional pro alpha 2(I) chains presents a unique opportunity to explore changes in collagen structure resulting from the complete (oim/oim mice) and partial (oim/+ mice) loss of functional alpha 2(I) chains. Tail tendon is a tissue with a well-defined, hierarchical organization of type I collagen. X-ray diffraction studies on oim/oim versus control tendons indicate that the total absence of alpha 2(I) chains results in a decrease in the order of axial packing and a loss of crystalline lateral packing. This suggests that the non-equivalence of three chains is an important determinant of lateral interactions between adjacent molecules and may be involved in the long-range axial order in type I collagen-containing tissues. Both homotrimeric and heterotrimeric type I collagen molecules are found in heterozygous oim mice and these appear to be present in the same co-polymeric fibrils, preventing crystalline lateral packing. In addition to these changes at a fibrillar level, the absence of the alpha 2(I) chain results in an increased enzymatic susceptibility at one site. The oim/oim mice are observed to have reduced body size and smaller tendon bundles, which may be a consequence of these molecular and fibrillar changes in collagen. Furthermore, it is Likely that a similar alteration in the molecular packing of collagen in bone fibrils contributes to the osteopenia and decreased bone strength in mice with the oim mutation that are also characteristic of human osteogenesis imperfecta. (C) 1997 Academic Press Limited.