Characterization of integrin β6 and thrombospondin-1 double-null mice
Characterization of integrin β6 and thrombospondin-1 double-null mice
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DOI：
10.1111/j.1582-4934.2005.tb00367.x
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发表时间：
2005-04-01
影响因子：
5.3
通讯作者：
Lawler, J
中科院分区：
文献类型：
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作者：
Ludlow, A;Yee, KO;Lawler, J
为了确定 TSP-1 和 α v beta 6 的重叠和非重叠功能，我们将 TSP-1 缺失和 β 6 缺失小鼠杂交，并将双缺失小鼠的表型与野生型和单缺失小鼠的表型进行比较。双无效小鼠表现出比野生型和单无效小鼠更严重的局灶性急性机化性肺炎，并且除肺以外的组织中炎症的发生率显着更高。暴露于脂多糖三天后，TSP-1 缺失和β 6 缺失小鼠的肺部粒细胞募集量增加了 5 至 8 倍。它们还具有野生型和单无效小鼠中罕见的异常，包括心脏变性（野生型小鼠为8.35％，双无效小鼠为28.1％）、胃腺上皮增生（野生型小鼠为2.8％，双无效小鼠为21.1％）和子宫内膜增生（野生型小鼠为0％，双无效雌性为38.5％）。此外，β6缺失和双缺失小鼠的良性和恶性癌症显着升高。胃乳头状瘤、耳和胃的鳞状细胞癌以及肺、阴道/子宫颈和结肠的腺癌的发生率最高。这些数据表明 TSP-1 和 alpha v beta 6 参与免疫系统和上皮稳态的调节。他们还表明，αvβ6 作为肿瘤抑制基因发挥作用，并且 TSP-1 和 αvβ6 激活 TGFβ 有助于正常组织结构和功能。
To identify overlapping and non-overlapping functions for TSP-1 and alpha v beta 6, we crossed TSP-1-null and beta 6-null mice and compared the phenotype of the double-null mice with those of wild-type and single-null mice. The double-null mice exhibited focal acute and organizing pneumonia that was more severe than the wild-type and single-null mice as well as a significantly higher incidence of inflammation in tissues other than the lung. The TSP-1-null and beta 6-null mice exhibited a five to eight-fold increase in granulocyte recruitment to the lung three days after exposure to lipopolysaacharide. They also had abnormalities that were infrequently observed in the wild-type and single-null mice, including heart degeneration (8.35% in wild-type and 28.1% in double-null mice), hyperplasia of the glandular epithelium of the stomach (2.8% in wild-type and 21.1% in double-null mice) and endometrial hyperplasia (0% in wild-type and 38.5% in double-null females). Furthermore, the beta 6-null and double-null mice displayed a significant elevation in benign and malignant cancers. Stomach papillomas, squamous cell carcinomas of the ear and stomach, and adenocarcinomas of the lungs, vagina/cervix and colon were observed with the highest frequency. These data demonstrate that TSP-1 and alpha v beta 6 are involved in regulation of the immune system and epithelial homeostasis. They also indicate that alpha v beta 6 functions as a tumor suppressor gene and that activation of TGF beta by TSP-1 and alpha v beta 6 contributes to normal tissue architecture and function.