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CLASS II GENES IN AUTOIMMUNE ANIMALS

自身免疫动物中的 II 类基因

基本信息

批准号：
2063808
负责人：
JOEL SCHIFFENBAUER
金额：
$ 18.11万
依托单位：
UNIVERSITY OF FLORIDA
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：
1990-09-01 至 1995-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2063808
关键词：
DNA MHC class II antigen autoimmunity electrophoresis genetic library genetic manipulation genetic regulatory element genetically modified animals laboratory mouse monoclonal antibody nucleic acid hybridization protein sequence protein structure function transcription factor transfection western blottings

项目摘要

The class II molecules play a central role in both normal and abnormal immune responses, and a number of autoimmune diseases both in man and mouse appear to be linked to class II molecules. We propose to evaluate the qualitative and quantitative contribution of the class II molecules from the NZW mouse strain to autoimmunity in the (NZWxNZB)F mouse. The qualitative structure function relationship of class II molecules in autoimmunity will be evaluated by seeking unusual sequences in NZW cDNA's. We will develop monoclonal antibodies specific for the NZW/NZB hybrid class II molecules to examine whether hybrid class II molecules exist in vivo, and determine if these hybrid molecules might contribute to the development of autoimmunity. Using transfections we will also determine whether the "u" haplotype is immunodominant, which would help explain the NZW contribution to accelerated autoimmunity. In addition, we plan to produce transgenic NZB mice, in which NZW class II transgenes are placed into NZB mice. To evaluate whether there is a quantitative contribution of class II molecules to autoimmunity, we will isolate NZB and NZW genes and examine both cis and trans acting factors which regulate the expression of class II genes. Cis acting factors will be evaluated by determining whether the 5' flanking region of the class II genes of NZW and NZB have unusual sequences. cDNA's encoding trans acting factors will be isolated by a Southwestern methodology whereby labeled oligonucleotides corresponding to the NZB and NZW 5' regulatory regions are used to probe NZB and NZW lambda gt11 libraries. These cDNA's will be examined for unusual sequences. These studies will evaluate both the quantitative and qualitative contributions of class II genes to autoimmunity.

II类分子在正常和异常的细胞中起着核心作用。免疫反应，以及许多自身免疫性疾病，小鼠似乎与II类分子有关。我们建议评估 II类分子的定性和定量贡献从NZW小鼠品系到（NZWxNZB）F小鼠中的自身免疫。的 II类分子的定性结构功能关系将通过寻找NZW cDNA中的不寻常序列来评价自身免疫。我们将开发单克隆抗体 NZW/NZB专用杂合II类分子以检查杂合II类分子是否存在于体内，并确定这些杂交分子是否有助于自身免疫的发展。通过转染，也确定“u”单倍型是否是免疫显性的，这将有助于解释NZW对加速自身免疫的贡献。另外我们计划生产转基因NZB小鼠，其中NZW II类转基因被放置植入NZB小鼠体内评价是否存在II类定量贡献分子自身免疫，我们将分离NZB和NZW基因，并检查顺式和反式作用因子调节类 II基因。顺式作用因子将通过确定 NZW和NZB的II类基因的5'侧翼区具有不寻常的序列的编码反式作用因子的cDNA将通过以下方法分离：西南方法学，其中标记的寡核苷酸对应于 NZB和NZW 5 ′调节区用于探测NZB和NZW λ gt 11库。将检查这些cDNA的异常序列。这些研究将从定量和定性两个方面进行评估。 II类基因对自身免疫的贡献。