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

A Mouse Model of Acrodermatitis Enteropathica

肠病性肢端皮炎小鼠模型

基本信息

批准号：
7469630
负责人：
GLEN K ANDREWS
金额：
$ 11.76万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-04-01 至 2008-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7469630
关键词：
A Mouse Acrodermatitis Address Affect Arabidopsis Biological Assay Biology Birds Breeding CCL21 gene Candidate Disease Gene Cell Line Cell membrane Cell physiology Cells Chromosome Mapping Code Complementary DNA Cultured Cells Dependence Dermatitis Dermatologic Detection Diarrhea Dietary Zinc Disease Embryonic Development Eukaryota Eukaryotic Cell Exons Experimental Animal Model Familial disease Family Gene Expression Gene Expression Regulation Gene Targeting Genes Genetic Genetic Recombination Globin Growth Histidine Homeostasis Human Human Genome Immune System Diseases In Vitro Individual Injection of therapeutic agent Intestinal Absorption Intestines Introns Ions Iron K562 Cells Knock-out Knockout Mice Laboratories Left Lesion Localized Location Mammals Mediating Membrane Messenger RNA Metabolism Metals Methodology Molecular Mucous Membrane Mus Mutate Mutation Names Nomenclature Northern Blotting Patients Physiological Plant Roots Play Process Promoter Regions Property Protein Biosynthesis Proteins Puromycin RNA Regulation Reporter Genes Resources Role Site Small Intestines Specificity Symptoms Testing Transcript Transfection Transgenes Transgenic Organisms Up-Regulation Weight Gain Yeasts ZIP protein Zinc Zinc Sulfate Zinc deficiency Zip Code acrodermatitis enteropathica autosomal recessive trait base blastocyst design embryonic stem cell expression vector homologous recombination in vivo inhibitor/antagonist insight knockout gene mRNA Stability member mouse model mutant novel promoter recessive genetic trait recombinase response uptake vector zinc-binding protein

项目摘要

The overall long-term objective of our studies is to elucidate the molecular mechanisms involved in zinc homeostasis in mammals. Herein, we propose to study the rare, autosomal recessive trait, acrodermatitis enteropathic (AE). AE results for the inability to absorb significant dietary zinc, and a candidate gene mutated in human patients with AE was just identified. This gene encodes a member of the ZIP gene superfamily of metal transporters and was named hZIP4. We will test the hypothesis that this putative zinc transporter plays a central physiological role in zinc homeostasis using the mouse model. No mouse models for AE exist and essentially nothing is known about the regulation and functions of ZIP4. In preliminary studies, we have cloned the mouse ZIP4 gene and cDNA, determined that it is highly expressed in the intestinal tract, and demonstrated that mZIP4 mRNA is dramatically up-regulated during periods of dietary zinc deficiency. Therefore, the specific aims of this proposal are to: 1) Delineate the metal transport properties of native and AE mutants of mZIP4; 2) elucidate the mechanisms of metallo-regulation of mZIP4 expression; and 3) determine the affects of targeted mutation of the mZIP4 gene on zinc homeostasis in the mouse. This project represents a collaborative effort between the laboratories of Drs. Andrews, Eide, and Peterson. The P.I., Dr. Andrews is an expert in mammalian embryonic development and zinc deficiency, and in metalloregulation of gene expression. The Co-I., Dr. Eide is an expert and leader in the field of ZIP transporter function and regulation, and Co-I., Dr. Peterson is an expert in globin locus regulation and mouse knockout strategies.

我们研究的总体长期目标是阐明所涉及的分子机制哺乳动物体内的锌稳态。在此，我们建议研究罕见的常染色体隐性特征，肠病性肢端皮炎（AE）。 AE 结果表明无法吸收大量膳食锌，并且人类 AE 患者中突变的候选基因刚刚被发现。该基因编码一个金属转运蛋白 ZIP 基因超家族的成员，被命名为 hZIP4。我们将测试假设这种假定的锌转运蛋白在锌稳态中发挥重要的生理作用使用鼠标模型。不存在 AE 的小鼠模型，并且基本上对 AE 一无所知 ZIP4的调节和功能。在初步研究中，我们克隆了小鼠ZIP4基因并 cDNA，确定其在肠道中高表达，并证明mZIP4 在膳食缺锌期间，mRNA 的表达显着上调。因此，该提案的具体目标是： 1) 描述天然和 AE 的金属传输特性 mZIP4 突变体； 2) 阐明mZIP4表达的金属调控机制；和 3) 确定 mZIP4 基因的靶向突变对小鼠锌稳态的影响。该项目代表了博士实验室之间的合作努力。安德鲁斯、艾德和彼得森.首席研究员安德鲁斯博士是哺乳动物胚胎发育和锌方面的专家缺陷以及基因表达的金属调节。联合主席艾德博士是一位专家和领导者 Peterson 博士是 ZIP 转运蛋白功能和调节领域的专家，也是珠蛋白领域的专家基因座调控和小鼠敲除策略。