Type III collagen is crucial for collagen I fibrillogenesis and for normal cardiovascular development
Type III collagen is crucial for collagen I fibrillogenesis and for normal cardiovascular development
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DOI：
10.1073/pnas.94.5.1852
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发表时间：
1997-03-04
影响因子：
11.1
通讯作者：
Jaenisch, R
中科院分区：
文献类型：
--
作者：
Liu, X;Wu, H;Jaenisch, R
III 型胶原蛋白是一种纤维形成胶原蛋白，包含三个 α1(III) 链，在早期胚胎和整个胚胎发生过程中表达。在成人中，III 型胶原蛋白是多种内脏和皮肤细胞外基质的主要成分。COL3A1 基因突变被认为是导致 IV 型埃勒斯-当洛斯综合征的原因，这种疾病会导致成年早期的主动脉破裂。为了直接研究Col3a1在发育和疾病中的作用，我们通过同源重组使胚胎干细胞中的Col3a1基因失活，突变的等位基因通过小鼠种系传播，纯合突变动物来自杂合杂交。大约10%的纯合突变动物存活到成年，但与野生型小鼠相比寿命要短得多。突变小鼠的主要死亡原因是主要血管破裂，类似于IV型埃勒斯-当洛斯综合征患者。对突变小鼠组织的超微结构分析表明，III 型胶原蛋白对于心血管系统和其他器官中正常的 I 型胶原纤维形成至关重要。
Type III collagen is a fibrilar forming collagen comprising three alpha 1(III) chains and is expressed in early embryos and throughout embryogenesis. In the adult, type III collagen is a major component of the extracellular matrix in a variety of internal organs and skin, Mutations in the COL3A1 gene have been implicated as a cause of type IV Ehlers-Danlos syndrome, a disease leading to aortic rupture in early adult life. To directly study the role of Col3a1 in development and disease, we have inactivated the Col3a1 gene in embryonic stem cells by homologous recombination, The mutated allele was transmitted through the mouse germ line and homozygous mutant animals were derived from heterozygous intercrosses. About 10% of the homozygous mutant animals survived to adulthood but have a much shorter life span compared with wild-type mice. The major cause of death of mutant mice was rupture of the major blood vessels, similar to patients with type IV Ehlers-Danlos syndrome. Ultrastructural analysis of tissues from mutant mice revealed that type III collagen is essential for normal collagen I fibrillogenesis in the cardiovascular system and other organs.