Pinson K I, Dunbar L, Samuelson L, Gumucio D L
Department of Anatomy and Cell Biology, University of Michigan, Ann Arbor 48109-0616, USA.
Dev Dyn. 1998 Jan;211(1):109-21. doi: 10.1002/(SICI)1097-0177(199801)211:1<109::AID-AJA10>3.0.CO;2-7.
The small intestine is functionally dependent on the presence of the brush border, a tightly packed array of microvilli that forms the amplified apical surface of absorptive cells. In the core of each microvillus, actin filaments are bundled by two proteins, villin and fimbrin. Previous in vitro studies using antisense approaches indicated that villin plays an important role in the morphogenesis of microvilli. To examine the in vivo consequences of villin deficiency, we disrupted the mouse villin gene by targeted recombination in mouse embryonic stem cells. A beta-galactosidase cDNA was also introduced into the villin locus by the targeting event. Homozygous villin-deficient mice are viable, fertile, and display no gross abnormalities. Intact microvilli are present in the small intestine, colon, kidney proximal tubules, and liver bile canaliculi. Although subtle ultrastructural abnormalities can be detected in the actin cores of small intestinal microvilli, localization of sucrase isomaltase, brush border myosin I, and zonula occludens I to the microvillar surface of the small intestine is normal. Thus, in vivo, villin plays a minor or redundant role in the generation of microvilli in multiple absorptive tissues.
小肠在功能上依赖于刷状缘的存在，刷状缘是由紧密排列的微绒毛组成的阵列，形成吸收细胞放大的顶端表面。在每个微绒毛的核心，肌动蛋白丝由两种蛋白质——绒毛蛋白和丝束蛋白捆绑在一起。先前使用反义方法的体外研究表明，绒毛蛋白在微绒毛的形态发生中起重要作用。为了研究绒毛蛋白缺乏在体内的后果，我们通过在小鼠胚胎干细胞中进行靶向重组来破坏小鼠绒毛蛋白基因。靶向事件还将β-半乳糖苷酶cDNA引入绒毛蛋白基因座。纯合绒毛蛋白缺陷小鼠是有活力的、可育的，并且没有明显的异常。完整的微绒毛存在于小肠、结肠、肾近端小管和肝胆小管中。尽管在小肠微绒毛的肌动蛋白核心中可以检测到细微的超微结构异常，但蔗糖酶异麦芽糖酶、刷状缘肌球蛋白I和紧密连接蛋白I在小肠微绒毛表面的定位是正常的。因此，在体内，绒毛蛋白在多种吸收组织中微绒毛的生成中起次要或冗余作用。
