Fatal bilateral chylothorax in mice lacking the integrin α9β1
Fatal bilateral chylothorax in mice lacking the integrin α9β1
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DOI：
10.1128/mcb.20.14.5208-5215.2000
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发表时间：
2000-07-01
影响因子：
5.3
通讯作者：
Sheppard, D
中科院分区：
文献类型：
--
作者：
Huang, XZ;Wu, JF;Sheppard, D
整合素家族成员的黏附受体介导细胞-细胞和细胞基质的相互作用，并已被证明在胚胎发育、伤口愈合、转移和其他生物过程中发挥重要作用。整合素α9β1是细胞外基质蛋白骨桥蛋白和张力素C以及细胞表面免疫球蛋白血管细胞黏附分子-1的受体。该受体广泛表达于平滑肌、肝细胞和一些上皮细胞。为了检测阿尔法9β1的体内功能，我们建立了缺乏阿尔法9亚单位表达的小鼠。阿尔法9亚单位基因零突变纯合子小鼠出生时看起来正常，但会出现呼吸衰竭，并在6至12天内死亡。呼吸衰竭是由大量积聚的胸液引起的，胸液中含有丰富的甘油三酯、胆固醇和淋巴细胞。阿尔法9(-/-)小鼠还会出现胸壁水肿和淋巴细胞渗透，似乎起源于淋巴管周围。Alpha 9蛋白在胚胎第14天在发育中的胸管中瞬时表达，但在发育的后期迅速消失。我们的结果表明，α9整合素是包括胸导管在内的淋巴系统正常发育所必需的，而α9缺乏可能是先天性乳糜胸的原因之一。
Members of the integrin family of adhesion receptors mediate both cell-cell and cell matrix interactions and have been shown to play vital roles in embryonic development, wound healing, metastasis, and other biological processes. The integrin alpha 9 beta 1 is a receptor for the extracellular matrix proteins osteopontin and tenacsin C and the cell surface immunoglobulin vascular cell adhesion molecule-1. This receptor is widely expressed in smooth muscle, hepatocytes, and some epithelia. To examine the in vivo function of alpha 9 beta 1, we have generated mice lacking expression of the alpha 9 subunit. Mice homozygous for a null mutation in the alpha 9 subunit gene appear normal at birth but develop respiratory failure and die between 6 and 12 days of age. The respiratory failure is caused by an accumulation of large volumes of pleural fluid which is rich in triglyceride, cholesterol, and lymphocytes. alpha 9(-/-) mice also develop edema and lymphocytic infiltration in the chest wall that appears to originate around lymphatics. alpha 9 protein is transiently expressed in the developing thoracic duct at embryonic day 14, but expression is rapidly lost during later stages of development. Our results suggest that the alpha 9 integrin is required for the normal development of the lymphatic system, including the thoracic duct, and that alpha 9 deficiency could be one cause of congenital chylothorax.