INVESTIGATION OF REGULATORY SEQUENCES IN THE PACAP-1 RECEPTER PROMOTER

PACAP-1 受体启动子中调控序列的研究

• 批准号: 7381417
• 负责人: KAREN L HINKLE
• 金额: $ 5.76万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381417
• 关键词: INVESTIGATION; REGULATORY; SEQUENCES; PACAP; RECEPTER

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Previous studies have shown that proper ion exchange and transport across the parietal cell membrane is essential for normal gastric acid secretion. For example, genetically engineered mice deficient for the Na+/H+ exchangers Nhe2 and Nhe4, the Cl-/HCO3 exchanger Ae2, and the K+ channel Kvlqt1 showed significant impairments in acid secretion. In addition, achlorhydric gastrin-deficient mice showed alterations in gastric expression of the water channel aquaporin-4 (Aqp4) and the chloride channel Clca3. The patterns of gastric expression of these genes during embryonic development or as mice age is unknown. Gastric acid secretion is thought to be initiated immediately before parturition; in addition, evidence suggests that there is an increase in gastric acid secretion as mice age. Understanding the expression patterns of Aqp4, Clca3, Nhe2, Nhe4, Ae2, Kir2.1, and Kvlqt1 both in development and in aging mice may yield clues as to the timing of initiation of acid secretion as well as the age-related increase in acid levels. The overall goal of this research is to analyze developmental and age-related expression of various channels and exchangers important for normal acid secretion, including Aqp4, Clca3, Nhe2, Nhe4, Ae2, Kir2.1, and Kvlqt1. The hypothesis of this study is that the gastric expression of these genes increases at later embryonic developmental stages and increases as adult mice age. Specific Aim 1 will focus on gene expression analysis and gastric immunolocalization of candidate molecules during embryonic development. Specific Aim 2 will analyze gene and protein expression patterns of these candidates in aging wild-type and gastrin-deficient mice. Determining the expression patterns of these genes in murine embryonic development as well as in aging mice will allow a more thorough understanding of mechanisms that that regulate the gastric acid secretory system. This research will have an impact on the field of gastrointestinal biology by further elucidating the developmental and age-related regulation of gastric acid secretion.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中得到体现。列出的机构是中心的机构，不一定是研究者的机构。先前的研究表明，适当的离子交换和跨壁细胞膜的运输对于正常的胃酸分泌至关重要。例如，缺乏 Na+/H+ 交换器 Nhe2 和 Nhe4、Cl-/HCO3 交换器 Ae2 和 K+ 通道 Kvlqt1 的基因工程小鼠显示出酸分泌的显着损害。此外，缺乏胃酸胃泌素的小鼠表现出水通道水通道蛋白-4 (Aqp4) 和氯通道 Clca3 胃表达的改变。这些基因在胚胎发育过程中或随着小鼠年龄的增长在胃中的表达模式尚不清楚。胃酸分泌被认为是在临产前开始的；此外，有证据表明，随着小鼠年龄的增长，胃酸分泌会增加。了解发育中和衰老小鼠中 Aqp4、Clca3、Nhe2、Nhe4、Ae2、Kir2.1 和 Kvlqt1 的表达模式可能会为酸分泌开始的时间以及与年龄相关的酸水平增加提供线索。本研究的总体目标是分析对正常酸分泌重要的各种通道和交换器的发育和年龄相关表达，包括 Aqp4、Clca3、Nhe2、Nhe4、Ae2、Kir2.1 和 Kvlqt1。这项研究的假设是，这些基因的胃表达在胚胎发育后期增加，并随着成年小鼠年龄的增长而增加。具体目标 1 将重点关注胚胎发育过程中候选分子的基因表达分析和胃免疫定位。具体目标 2 将分析这些候选者在衰老野生型和胃泌素缺陷小鼠中的基因和蛋白质表达模式。确定这些基因在小鼠胚胎发育以及衰老小鼠中的表达模式将有助于更彻底地了解调节胃酸分泌系统的机制。这项研究将通过进一步阐明胃酸分泌的发育和年龄相关调节，对胃肠生物学领域产生影响。