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STRUCTURE AND EXPRESSION OF COMPLEMENT GENES C3 AND C4

补体基因C3和C4的结构和表达

基本信息

批准号：
3129007
负责人：
GEORG H FEY
金额：
$ 17.7万
依托单位：
SCRIPPS CLINIC AND RESEARCH FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-01-01 至 1988-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3129007
关键词：
alleles chromosome complement gel electrophoresis gene expression genetic manipulation genetic mapping genetic transcription genome hepatocellular carcinoma human tissue immune response genes immunodeficiency inflammation macrophage messenger RNA molecular cloning nucleic acid sequence tissue /cell culture

项目摘要

The project proposes to study (a) the structure of the gene encoding complement protein C3, (b) the controls of transcription of this gene into RNA, (c) the molecular defects that lead to inherited C3 deficiencies in man and (d) the isolation of mouse cDNA. The study will take advantage of mouse C3 cDNA clones and C3 genomic DNA clones that have been prepared in the applicant's laboratory and will extend currently ongoing work. First, the tissue specific expression of C3 will be investigated. C3 mRNA concentrations will be titrated in hepatocytes, macrophages and in a variety of C3 producing and non-producing tissue culture cell lines and correlated with the state of methylation of the gene. The 5'-ends of liver and macrophage C3 mRNAs will be compared in order to determine whether the gene is transcribed in both tissues from the same promoter. It is intended to establish the total nucleotide sequence of C3 mRNA as a basis for future studies of particular regions of the C3 polypeptide, such as the binding sites for cellular C3d receptors. The second part proposes to isolate one intact copy of the human C3 gene from a gene library to be constructed in cosmid vectors. The human gene will be characterized and assayed for function by transfection into tissue culture cells. A defective allele carried by homozygous C3 deficient members of a Dutch family will be analyzed. In the third part an approach is described for the production of cloned mouse C4 cDNA clones. The last section outlines how C4 cDNA clones will be characterized and distinguished from cDNA clones for the C4 variant of mice, the Slp-protein. These clones will be used to screen mouse gene libraries for C4 genomic clones. Work on the human C4 gene will follow according to the initial results obtained with the mouse C4 gene. The proposed studies on the C3 and C4 genes will provide basic information on the structure and the regulation of these genes and also on inherited human disorders associated with these genes.

该项目拟研究（a）基因编码的结构补体蛋白 C3，(b) 该基因转录的控制 RNA，(c) 导致遗传性 C3 缺陷的分子缺陷人和 (d) 小鼠 cDNA 的分离。该研究将利用小鼠 C3 cDNA 克隆和 C3 基因组 DNA 克隆已在申请人的实验室并将扩展目前正在进行的工作。第一的，将研究C3的组织特异性表达。 C3 mRNA 浓度将在肝细胞、巨噬细胞和多种产生和不产生 C3 的组织培养细胞系和与基因的甲基化状态相关。肝脏的5'端将比较巨噬细胞 C3 mRNA，以确定是否基因在两种组织中从同一启动子转录。其目的是建立C3 mRNA的总核苷酸序列作为未来的基础 C3 多肽特定区域的研究，例如结合细胞 C3d 受体位点。第二部分建议隔离一个来自要构建的基因库的人类 C3 基因的完整副本粘粒载体。人类基因将被表征和分析通过转染到组织培养细胞中发挥作用。有缺陷的等位基因由荷兰家庭的纯合 C3 缺陷成员携带分析了。第三部分描述了一种生产方法克隆小鼠 C4 cDNA 克隆。最后一节概述了 C4 cDNA 如何克隆将与 C4 变体的 cDNA 克隆进行表征和区分小鼠的Slp-蛋白。这些克隆将用于筛选小鼠基因 C4 基因组克隆文库。人类 C4 基因的研究工作将随之而来根据小鼠 C4 基因获得的初步结果。这拟议的 C3 和 C4 基因研究将提供以下基本信息这些基因的结构和调控以及遗传性人类与这些基因相关的疾病。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Relationships between the gene and protein structure in human complement component C9.

人补体成分C9基因与蛋白质结构的关系。

DOI：
10.1021/bi00417a050
发表时间：
1988
期刊：
Biochemistry
影响因子：
2.9
作者：
Marazziti,D;Eggertsen,G;Fey,GH;Stanley,KK
通讯作者：
Stanley,KK

Amino acid sequences of mouse complement C3 derived from nucleotide sequences of cloned cDNA.

小鼠补体 C3 的氨基酸序列源自克隆 cDNA 的核苷酸序列。

DOI：
10.1111/j.1749-6632.1983.tb18118.x
发表时间：
1983
期刊：
Annals of the New York Academy of Sciences
影响因子：
5.2
作者：
Fey,GH;Wiebauer,K;Domdey,H
通讯作者：
Domdey,H

Structure and expression of the C3 gene.

C3基因的结构和表达。

DOI：
10.1007/bf00205869
发表时间：
1983
期刊：
Springer seminars in immunopathology
影响因子：
0
作者：
Fey,G;Domdey,H;Wiebauer,K;Whitehead,AS;Odink,K
通讯作者：
Odink,K

Human complement component C3: cDNA coding sequence and derived primary structure.

DOI：
10.1073/pnas.82.3.708
发表时间：
1985-02
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
M. D. Bruijn;Georg H. Fey
通讯作者：
M. D. Bruijn;Georg H. Fey