EMBRYONIC AND AGE-RELATED EXPRESSION OF AQP4, NHE2, AE2, KIR21 AND KVIQT1 IN TH

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 以前的研究表明，适当的离子交换和跨壁细胞膜的运输是正常的胃酸分泌所必需的。例如，缺乏Na+/H+交换器Nhe 2和Nhe 4、Cl-/HCO 3交换器Ae 2和K+通道Kvlqt 1的基因工程小鼠表现出酸分泌的显著损伤。此外，无胃酸胃泌素缺陷小鼠表现出胃水通道水通道蛋白4（Aqp 4）和氯离子通道Clca 3的表达改变。这些基因在胚胎发育过程中或随着小鼠年龄增长而在胃中表达的模式尚不清楚。胃酸分泌被认为是在分娩前立即开始的;此外，有证据表明，随着小鼠年龄的增长，胃酸分泌增加。了解Aqp 4，Clca 3，Nhe 2，Nhe 4，Ae 2，Kir2.1和Kvlqt 1在发育和衰老小鼠中的表达模式可能会产生关于酸分泌起始时间以及与年龄相关的酸水平增加的线索。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Aqp 4，Clca 3，Nhe 2，Nhe 4，Ae 2，Kir2.1和Kvlqt 1。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将集中在胚胎发育过程中的候选分子的基因表达分析和胃免疫定位。具体目标2将分析这些候选人在老龄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，将使我们更深入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道生物学领域产生影响。

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.