Lu Hong, Zimek Alexander, Chen Jian, Hesse Michael, Büssow Heinrich, Weber Klaus, Magin Thomas M
Institut für Physiologische Chemie, Abteilung für Zellbiochemie, Bonner Forum Biomedizin and LIMES, Rheinische Friedrich-Wilhelms-Universität, Nussallee 11, D-53115 Bonn, Germany.
Eur J Cell Biol. 2006 Aug;85(8):803-11. doi: 10.1016/j.ejcb.2006.04.001. Epub 2006 Jun 8.
We have recently demonstrated that the keratin K3 gene, which is active in the suprabasal human corneal epithelium, is missing in the genome of the mouse. We show that a normal K3 gene exists in a wide variety of mammals while in rodents the gene is converted to a pseudogene with a very strong sequence drift. The availability of K5-/- mice provides a unique opportunity to investigate type-specific keratin function during corneal differentiation in the absence of both K5 and K3. Here, we report that the deletion of K5, which in wild-type mice forms a cytoskeleton with K12, does neither cause keratin aggregation nor cytolysis in the cornea. This is due to the induction of K4 in corneal epithelial cells, normally restricted to corneal stem stem cells residing in the limbus. Using a combination of antibodies and RT-PCR, we identified additional keratins expressed in the mouse cornea including K23 which was previously thought to be specific for pancreatic carcinomas. This reflects an unexpected complexity of keratin expression in the cornea. Our data suggest that in the absence of mechanical stress, corneal differentiation does not depend on distinct keratin pairs, supporting a concept of functional redundancy, at least for certain keratins.
我们最近证明，在人角膜上皮基底上层活跃的角蛋白K3基因，在小鼠基因组中缺失。我们发现，在多种哺乳动物中存在正常的K3基因，而在啮齿动物中该基因已转变为具有非常强烈序列漂移的假基因。K5基因敲除小鼠的存在为研究在缺乏K5和K3的情况下角膜分化过程中特定类型角蛋白的功能提供了独特的机会。在此，我们报告，在野生型小鼠中与K12形成细胞骨架的K5基因缺失，在角膜中既不会导致角蛋白聚集也不会引起细胞溶解。这是由于角膜上皮细胞中K4的诱导，K4通常局限于位于角膜缘的角膜干细胞。通过抗体和逆转录聚合酶链反应相结合的方法，我们鉴定出在小鼠角膜中表达的其他角蛋白，包括先前认为对胰腺癌具有特异性的K23。这反映了角膜中角蛋白表达存在意想不到的复杂性。我们的数据表明，在没有机械应力的情况下，角膜分化不依赖于特定的角蛋白对，这支持了至少对于某些角蛋白而言功能冗余的概念。
