权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

DEVELOPMENTAL REGULATION OF GASTRIN GENE EXPRESSION

胃泌素基因表达的发育调控

基本信息

批准号：
2133576
负责人：
Timothy Cragin Wang
金额：
$ 8.74万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-01-01 至 1994-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2133576
关键词：
autocrine cell differentiation gastrins gene expression genetic regulation genetically modified animals human tissue laboratory mouse mammalian embryology pancreatic islets protooncogene regeneration transcription factor

项目摘要

A number of observations suggest that gastrin may play a role in regulation pancreatic development. Gastrin is transiently expressed in the pancreas during early fetal development corresponding to a time of rapid proliferation of islet cells. In addition, pancreatic gastrin is selectively repressed after birth when the mature, pancreatic islets have little capacity for further proliferation or regeneration. Furthermore, gastrin has recently been shown to act as an autocrine growth factor in vitro for some islet cell lines. The activity of the gastrin promoter in islet cells depends on a cis-acting islet cell specific DNA element similar to the insulin enhancer. Upstream of the insulin enhancer-like element is a silencer element, identical to part of the B-interferon negative regulatory domain, to which a trans-acting repressor binds to inhibition gastrin gene transcription. In vivo competition and DNA transfection studies will be used to demonstrate that the gastrin promoter is activated in islet cells by the same islet cell specific transcription factor which activates the insulin gene. Binding of the insulin transactivator to the insulin enhancer-like element will also be shown using mobility shift assays and methylation interference studies. Gastrin transgenes containing deletions of the insulin enhancer-like domain will be inserted into the germline of mice to determine if this abolishes pancreatic expression during fetal development. Analysis of the developmental expression of gastrin transgenes containing deletions of the B-interferon-like negative element should provide insights into the role of the negative element in mediating the postnatal extinction of pancreatic gastrin expression. Further, the transgenic approach should define the role of gastrin as an islet cell growth factor. The effect of oncogenes and growth factors on repressor activity will also be investigated in order to elucidate the mechanism through which proto- oncogenes regulate islet cell differentiation. Overall, these studies on the regulation of the gastrin promoter provide an approach to analyze the molecular events that regulate islet cell differentiation. Understanding these events may lead to ways of improving islet cell regeneration.

大量观察结果表明胃泌素可能在调节中发挥作用胰腺发育。胃泌素在胰腺中短暂表达在胎儿早期发育期间，对应于快速发育时期胰岛细胞增殖。此外，胰胃泌素出生后，当成熟的胰岛具有选择性抑制进一步增殖或再生的能力很小。此外，胃泌素最近被证明可以作为自分泌生长因子一些胰岛细胞系的体外。胃泌素启动子的活性胰岛细胞依赖于顺式作用的胰岛细胞特定的 DNA 元件，类似于至胰岛素增强剂。胰岛素增强剂样元件的上游是消音器元件，与 B-干扰素阴性部分相同调节结构域，反式作用阻遏物与其结合从而产生抑制作用胃泌素基因转录。体内竞争和 DNA 转染研究将用于证明胃泌素启动子在胰岛细胞中被激活激活胰岛素的相同胰岛细胞特异性转录因子基因。胰岛素反式激活因子与类胰岛素增强剂的结合还将使用迁移率变化分析和甲基化来显示元素干扰研究。含有缺失的胃泌素转基因胰岛素增强子样结构域将被插入小鼠种系中确定这是否会消除胎儿发育过程中的胰腺表达。含有胃泌素转基因的发育表达分析 B-干扰素样阴性元件的缺失应该可以提供一些见解探讨消极因素在介导后天灭绝中的作用胰腺胃泌素的表达。此外，转基因方法应定义胃泌素作为胰岛细胞生长因子的作用。的效果癌基因和生长因子对抑制活性的影响也将被研究目的是为了阐明原型的机制癌基因调节胰岛细胞分化。总体而言，这些研究胃泌素启动子的调节提供了一种分析方法调节胰岛细胞分化的分子事件。理解这些事件可能会导致改善胰岛细胞再生的方法。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A rat gastrin-human gastrin chimeric transgene directs antral G cell-specific expression in transgenic mice.

大鼠胃泌素-人胃泌素嵌合转基因指导转基因小鼠胃窦 G 细胞特异性表达。

DOI：
10.1152/ajpgi.1995.268.6.g1025
发表时间：
1995
期刊：
The American journal of physiology.
影响因子：
0
作者：
Wang,TC;Babyatsky,MW;Oates,PS;Zhang,Z;Tillotson,L;Chulak,M;Brand,SJ;Schmidt,EV
通讯作者：
Schmidt,EV

HEPATOCYTE GROWTH-FACTOR IN TRANSGENIC MICE - EFFECTS ON HEPATOCYTE GROWTH, LIVER-REGENERATION AND GENE-EXPRESSION