Madison Blair B, Dunbar Laura, Qiao Xiaotan T, Braunstein Katherine, Braunstein Evan, Gumucio Deborah L
Department of Cell and Developmental Biology, The University of Michigan Medical School, Ann Arbor, Michigan 48109-0616, USA.
J Biol Chem. 2002 Sep 6;277(36):33275-83. doi: 10.1074/jbc.M204935200. Epub 2002 Jun 13.
Villin, an actin bundling protein found in the apical brush border of absorptive tissues, is one of the first structural genes to be transcriptionally activated in the embryonic intestinal endoderm. In the adult, villin is broadly expressed in every cell of the intestinal epithelium on both the vertical axis (crypt to villus tip) and the horizontal axis (duodenum through colon) of the intestine. Here, we document that a 12.4-kilobase region of the mouse villin gene drives high level expression of two different reporter genes (LacZ and Cre recombinase) within the entire intestinal epithelium of transgenic mice. Deletion of a portion of this transgene results in reduction of beta-galactosidase activity in restricted domains of the small intestine (duodenum) and large intestine (cecum). In addition, expression is reduced in the crypt compartment throughout the intestine. Thus, the global expression pattern of villin in the intestine is apparently the consequence of an amalgam of distinct and individual domain-specific control processes. That is, expression of villin in the duodenum and cecum requires different regulatory sequences than the rest of the intestine, and the expression of villin in crypts is regulated by different circuitry than expression of villin on villus tips.
绒毛蛋白是一种肌动蛋白成束蛋白，存在于吸收性组织的顶端刷状缘，是胚胎肠内胚层中最早被转录激活的结构基因之一。在成体中，绒毛蛋白在肠道垂直轴（隐窝至绒毛顶端）和水平轴（从十二指肠到结肠）的肠上皮的每个细胞中广泛表达。在此，我们证明小鼠绒毛蛋白基因的一个12.4千碱基区域可驱动转基因小鼠整个肠上皮内两种不同报告基因（LacZ和Cre重组酶）的高水平表达。缺失该转基因的一部分会导致小肠（十二指肠）和大肠（盲肠）特定区域的β-半乳糖苷酶活性降低。此外，整个肠道隐窝区的表达都会降低。因此，绒毛蛋白在肠道中的整体表达模式显然是不同的、特定区域的控制过程混合的结果。也就是说，绒毛蛋白在十二指肠和盲肠中的表达需要与肠道其他部位不同的调控序列，并且绒毛蛋白在隐窝中的表达由与绒毛顶端的绒毛蛋白表达不同的调控机制调控。
