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Neurogenin3 and Intestinal Failure

Neurogenin3 和肠衰竭

基本信息

批准号：
8303422
负责人：
MARTIN G MARTIN
金额：
$ 32.83万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8303422
关键词：
Ablation Adult Alpha-mannosidase Apical Applications Grants Assimilations Birth Brush Border Cell Cycle Arrest Cell Differentiation process Cell Line Cell Proliferation Cells Characteristics Child Chronic Clinical Collection Data Defect Development Diarrhea Diphtheria Toxin Disease Endocrine Enhancers Enteral Enterocytes Enteroendocrine Cell Enzymes Failure Functional disorder Genes Germ-Line Mutation Goals Grant Health Helix-Loop-Helix Motifs Hereditary Disease Hormones Human Hybrids Impairment Intestinal Diseases Intestines Ions Islet Cell Knockout Mice Laboratories Life Malabsorption Syndromes Mediating Molecular Mouse Cell Line Movement Mus Mutation Names Neonatal Nutrient Pancreas Pathologic Patients Physiological Process Proteins Role Salts Series Stem cells Stream System Testing Work Yeasts absorption apical membrane attenuation base clinical phenotype gut endocrine cell improved inhibitor/antagonist insight islet migration mortality mouse Neurog3 protein novel research study transcription factor uptake

项目摘要

LAY ABSTRACT A small but significant percentage of children are born with severe life threatening diarrhea that can be classified as congenital. These children frequently have one of a growing group of genetic disorders that generally result in improper movement of various nutrients and salts across the intestine. We have recently discovered that a group of children who are incapable to absorbing all forms of nutrients have a genetic disorder that results in the inability to form enteroendocrine cells. Enteroendocrine cells are the hormone producing cells that reside in the gut and their formation is driven by a gene named Neurogenin3 that is defective in these children. In this grant application, we propose to identify more children with defects in the NEUROGENIN-3 gene so that we can get a better understanding of the clinical implications of this disorder. We also have been working on mice that carry a similar mutation of the NEUROGENIN-3 gene and we're using it to isolate the early and late forms of enteroendocrine cells in mice and humans. One main goal is to isolate these cells is so that we can get a better understanding of how they work, and how subsets of these cells develop. We have also found that NEUROGENIN-3 causes enteroendocrine cells that are grown in the laboratory to stop dividing and to take on the characteristics of mature enteroendocrine cells. We hope to understand the mechanism of how NEUROGENIN-3 causes the cells to stop dividing and to determine if a similar process is occurring in live mice. Finally, we have evidence that a loss of enteroendocrine cells results in a dysfunction of the intestinal cells called enterocytes that are responsible for absorbing nutrients. Here we plan a series of experiments to begin understanding the mechanism of how an absence of enteroendocrine cells leads to improper handling of nutrients by the enterocytes.

简单摘要一小部分但很大比例的儿童出生时患有严重的危及生命的腹泻，被归类为先天性。这些孩子经常患有一组不断增长的遗传疾病，通常导致各种营养物质和盐在肠道中的不适当移动。我们最近研究发现，一群无法吸收所有形式营养的儿童有一种遗传缺陷，导致不能形成肠内分泌细胞的疾病。肠内分泌细胞是产生驻留在肠道中的细胞，它们的形成是由一种名为Neurogenin 3的基因驱动的，有缺陷的孩子在这项拨款申请中，我们建议识别更多在以下方面有缺陷的儿童： NEUROGENIN-3基因，以便我们能够更好地了解这种疾病的临床意义。我们也一直在研究携带神经生成素-3基因类似突变的小鼠，用它来分离小鼠和人类的早期和晚期肠内分泌细胞。一个主要目标是分离这些细胞是为了让我们更好地了解它们是如何工作的，以及这些细胞的子集是如何工作的。细胞发育。我们还发现，神经生成素-3导致肠内分泌细胞生长在肠上皮细胞中。实验室停止分裂并呈现成熟肠内分泌细胞的特征。我们希望了解神经生成素-3如何导致细胞停止分裂的机制，并确定是否存在神经生成素-3。类似的过程也发生在活老鼠身上。最后，我们有证据表明，肠内分泌细胞的损失导致肠细胞的功能障碍，肠细胞负责吸收营养。这里我们我计划进行一系列的实验，开始了解缺乏肠内分泌的机制，细胞导致肠上皮细胞对营养物的不当处理。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Novel Homozygous Inactivating Mutation in the PCSK1 Gene in an Infant with Congenital Malabsorptive Diarrhea.

DOI：
10.3390/genes12050710
发表时间：
2021-05-10
期刊：
Genes
影响因子：
3.5
作者：
Aerts L;Terry NA;Sainath NN;Torres C;Martín MG;Ramos-Molina B;Creemers JW
通讯作者：
Creemers JW

Origin of the brush cell lineage in the mouse intestinal epithelium.

DOI：
10.1016/j.ydbio.2011.12.009
发表时间：
2012-02-15
期刊：
Developmental biology
影响因子：
2.7
作者：
Bjerknes M;Khandanpour C;Möröy T;Fujiyama T;Hoshino M;Klisch TJ;Ding Q;Gan L;Wang J;Martín MG;Cheng H
通讯作者：
Cheng H

Application of Whole Exome Sequencing in Congenital Secretory Diarrhea Diagnosis.

整个外显子组测序在先天性分泌性腹泻诊断中的应用。

DOI：
10.1097/mpg.0000000000002258
发表时间：
2019-06
期刊：
Journal of pediatric gastroenterology and nutrition
影响因子：
2.9
作者：
Gupta A;Sanville J;Menz T;Warner N;Muise AM;Fiedler K;Martín MG;Padbury J;Phornphutkul C;Sanchez-Esteban J;Cerezo CS
通讯作者：
Cerezo CS

Congenital diarrhoeal disorders: advances in this evolving web of inherited enteropathies.