REGULATION OF INTESTINAL BILE ACID BINDING PROTEIN

申请者是儿科胃肠病学三年级研究员， 对研究肠道基因调控和发育感兴趣 获得学术医学研究生涯所需的技能。 该提案的重点是肠道胆汁酸结合蛋白。 (IBABP)，一种被认为与胆汁酸有关的胞浆蛋白 (Ba)肠肝循环(EHC)的吸收成分。 这个系统维持着BAP池，因此对血脂是必不可少的 消化和吸收。IBABP基因在啮齿动物体内的表达 出生后第三周，与其他发育相吻合的时间 EHC的一部分，如回肠顶端转运蛋白(ASBT) 肝脏BA合成。这项为期5年的奖励将提供丰富的 应聘者的~S通过调研研究事业发展 回肠标志IBABP的调节可能提供洞察力 EHC和肠道发育。最初，生理学研究 将确定鲁米那BA和糖皮质激素(GC)在 哺乳大鼠IBABP和ASBT基因表达水平。有没有可能 IBABP和ASBT表达的开始是由一种内在的 时间机制将通过移植胎鼠回肠来检验。 变成免疫缺陷的小鼠。在这种模式中，缺少 流明因子和正常荷尔蒙变化发生在 发育中的大鼠。转录变化对基因的作用 IBABP mRNA在正常发育过程中的稳态水平升高 而BA和GC的诱导将通过核运行进行评估 化验。随后，内在机制将进一步 在细胞水平上定义为内胚层/间充质层分离 和重新关联。在他的实验室里学习这项技术。 米歇尔·凯丁格代表着一个成为行家的宝贵机会 这是一项在美国没有做到的技能。最后，老鼠 将分离IBABP基因并对其进行鉴定，以便顺式作用 调节本源基因调控的元件可以通过 体外转基因和体内转基因小鼠研究。Dr。 苏珊·亨宁的实验室，其主要研究对象是肠道 发展，是发展这一点的良好环境 求婚。因为婴儿对BA的吸收也是不成熟的 与哺乳大鼠一样，该项目可能为临床应用提供 管理新生儿，特别是早产儿。

A third-year fellow in pediatric gastroenterology, the applicant is interested in investigating intestinal gene regulation and developing the skills needed to attain a research career in academic medicine. The focus of the proposal is the intestinal bile acid binding protein (IBABP), a cytosolic protein believed to be involved in the bile acid (BA) absorption component of the enterohepatic circulation(EHC). This system maintain the BAP pool and thus is essential to lipid digestion and absorption. IBABP mRNA appears in rodents during the third postnatal week, a time coincident with the development of other parts of the EHC such as the apical transporter (ASBT) in the ileum and hepatic BA synthesis. This 5-yr award will provide enrichment of the applicant~s research career development through investigating the regulation of IBABP, an ileal marker which may provide insight into EHC and intestinal development. Initially, physiologic studies will determine the roles of luminal BA and gluco-corticoids (GC) on IBABP and ASBT mRNA levels in suckling rats. The possibility that the onset of IBABP and ASBT expression is controlled by an intrinsic timing mechanism will be examined by grafting fetal rat ileum s.c. into immune-deficient mice. In this model there is absence of luminal factors and the normal hormonal changes that occur in the developing rat. The contribution of transcriptional changes to the increased steady-state levels of IBABP mRNA during normal development and with BA and GC induction will be assessed by nuclear run-on assays. Subsequently, the intrinsic mechanism will be further defined at the cellular level with endoderm/mesenchyme dissociation and reassociations. Learning this technique in the laboratory of Dr. Michele Kedinger represents an invaluable opportunity to become adept at a skill which is not done in the United States. Finally, the rat IBABP gene will be isolated and characterized so that the cis-acting elements which mediate onto-genic regulation can be located through in vitro tranfections and in vivo transgenic mouse studies. Dr. Susan Henning's laboratory, whose primary focus is intestinal development, is an excellent environment in which to develop this proposal. Because BA absorption is immature in human infants as well as in suckling rats, this project may provide clinical application to managing neonates, especially those who are premature.