Analysis of ABCA Transporter Function in Homologous Recombinant Mice

同源重组小鼠 ABCA 转运蛋白功能分析

基本信息

批准号：
7255784
负责人：
MASON W FREEMAN
金额：
$ 51.59万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7255784
关键词：
ABCA3 gene ATP-Binding Cassette Transporters Aging-Related Process Animal Model Antibodies Apolipoproteins Applications Grants Bacterial Artificial Chromosomes Binding Biological Biological Process Biology Blindness Cell membrane Cells Cholesterol Cholesterol Homeostasis Class Communities Coupled Cystic Fibrosis Data Development Discipline Disease ES Cell Line Family Family member Fluorescent in Situ Hybridization Gene Expression Generations Genes Genomics Goals Grant Grouping Heart Diseases Hereditary Disease High Density Lipoproteins Histology Human In Vitro Integral Membrane Protein Ions Knockout Mice Laboratories Lead Length Link Lipids Macular degeneration Maps Measurement Membrane Methods Molecular Profiling Mus Mutation Neonatal Oligonucleotide Microarrays Pathway interactions Peripheral Nervous System Diseases Phospholipids Physiology Play Prevention Progressive intrahepatic cholestasis Proteins Pseudoxanthoma Elasticum Reagent Recombinants Research Research Design Research Personnel Respiratory Failure Retina Retinal Degeneration Role Spottings Stem cells Tangier Disease Technology Technology Assessment Tissue Microarray Tissues Tonsil Work embryonic stem cell expectation genome sequencing high throughput technology human disease in vivo insight leukodystrophy liquid chromatography mass spectrometry member novel programs skin disorder therapeutic target tool vector virtual

项目摘要

DESCRIPTION (Provided by applicant): The ATP-binding cassette (ABC) transporters compose one of the largest and most important families of transmembrane proteins in the biological kingdom. Within the ABC family is a group of molecules that are referred to as A class transporters that share substantial sequence similarity. The ABCA class molecules comprise twelve proteins of which only two, ABCA1 and ABCA4, have a clearly defined function. This grant proposes to generate homologous recombinant mice lacking each of the other ten A class ABCA transporters and to characterize the resulting functional deficit in the homologous recombinant mice. A novel recombinant bacterial artificial chromosome technology will be used to produce the targeting vectors and fluorescence-in-situ hybridization will be utilized to identify correctly targeted embryonal stem cell clones. Characterization of the null mice will employ high-throughput technologies including liquid chromatography mass spectrometry analysis of tissue lipids and spotted oligonucleotide microarray measurements of gene expression. All of the reagents generated in this work, including null mice, full-length expression cDNAs, and anti-ABCA1 antibodies will be made available to the research community so that other investigators can exploit them in order to facilitate our understanding of the role these ABCA transporters play in human physiology and disease.

描述（由申请人提供）：ATP结合盒（ABC）转运蛋白是生物王国中最大，最重要的跨膜蛋白家族之一。在ABC家族中，是一组分子，被称为具有具有实质序列相似性的类转运蛋白。 ABCA类分子包含十二种蛋白质，其中只有两种ABCA1和ABCA4具有明确定义的功能。该赠款建议生成缺乏其他十种A级ABCA转运蛋白的同源重组小鼠，并表征同源重组小鼠中所得的功能不足。一种新型的重组细菌人造染色体技术将用于产生靶向载体，将使用原位杂交荧光来识别正确靶向靶向的胚胎干细胞克隆。零小鼠的表征将采用高通量技术，包括组织脂质的液相色谱质谱分析和基因表达的斑点寡核苷酸微阵列测量。这项工作中产生的所有试剂，包括无效小鼠，全长表达cDNA和抗ABCA1抗体，将提供给研究界的抗体，以便其他研究人员可以利用它们，以促进我们对这些ABCA转运蛋白在人类生理学和疾病中发挥的作用的理解。