The α2 integrin subunit-deficient mouse -: A multifaceted phenotype including defects of branching morphogenesis and hemostasis
The α2 integrin subunit-deficient mouse -: A multifaceted phenotype including defects of branching morphogenesis and hemostasis
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DOI：
10.1016/s0002-9440(10)64185-5
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发表时间：
2002-07-01
影响因子：
6
通讯作者：
Zutter, MM
中科院分区：
文献类型：
--
作者：
Chen, JC;Diacovo, TG;Zutter, MM
α(2)β(1) 整联蛋白是在血小板、内皮细胞、成纤维细胞和上皮细胞上表达的胶原蛋白/层粘连蛋白受体。为了确定α(2)β(1)整合素在体内的作用，我们创建了一种基因工程小鼠，其中α(2)β(1)整合素的表达被完全消除。缺乏α(2)β(1)整合素的小鼠能够存活、具有生育能力并且发育正常，纯合子没有过度致死率。在 α(2) 缺失小鼠中，α(2)β(1) 整合素蛋白和 α(2) mRNA 均检测不到。对心脏、肺、肾脏、胃肠道、胰腺、皮肤和生殖道的大体和组织学评估未发现异常。然而，乳腺分支形态发生的定量分析表明，α(2) 缺陷动物的分支复杂性显着降低。对α(2) 缺陷动物的研究并不支持α(2)β(1)、整联蛋白在伤口加热中对成纤维细胞和角质形成细胞的作用。与野生型同窝小鼠的血小板相比，α(2) 缺失小鼠的血小板在静态或剪切应力条件下均无法粘附到 I 型胶原上。尽管来自 α(2) 缺陷动物的血小板会响应胶原蛋白而聚集，但其聚集的滞后时间较长且强度较低。 α(2)β(1) 整合素无效。因此，小鼠表现出多种、有时微妙的表型，与α(2)β(1)整合素表达的广泛模式一致。
The alpha(2)beta(1) integrin is a collagen/laminin receptor expressed on platelets, endothelial cells, fibroblasts, and epithelial cells. To define the role of the alpha(2)beta(1) integrin in vivo, we created a genetically engineered mouse in which expression of the alpha(2)beta(1) integrin was completely eliminated. Mice deficient in the alpha(2)beta(1), integrin are viable, fertile, and develop normally with no excess lethality of homozygotes. Both alpha(2)beta(1)-integrin protein and alpha(2) mRNA were undetectable in the alpha(2)-null mice. Gross and histological evaluation of the heart, lungs, kidneys, gastrointestinal tract, pancreas, skin, and reproductive tracts revealed no abnormalities. However, quantitative analysis of mammary gland branching morphogenesis demonstrated that branching complexity is markedly diminished in the alpha(2)-deficient animals. Studies in the alpha(2)-deficient animals do not support the proposed roles for the alpha(2)beta(1), Integrin on fibroblasts and keratinocytes in wound heating. When compared to platelets from wild-type littermates, platelets from alpha(2)-null mice failed to adhere to type I collagen under either static or shear-stress conditions. Although platelets from alpha(2)-deficient animals aggregated in response to collagen, they did so with prolonged lag time and lessened intensity. The alpha(2)beta(1) integrin-null. mouse thus exhibits diverse, sometimes subtle, phenotypes consistent with the widespread pattern of alpha(2)beta(1) integrin expression.