DUCK ANTIBODY GENES--UNUSUAL ORGANIZATION AND EXPRESSION

鸭抗体基因——异常的组织和表达

• 批准号: 6170893
• 负责人: GREGORY W WARR
• 金额: $ 24.5万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6170893
• 关键词: B lymphocyte; antibody formation; ducks; gene expression; gene rearrangement; genetic mapping; immunoglobulin A; immunoglobulin genes; molecular cloning; nucleic acid sequence

The duck's immune system functions poorly, and has been described as inept. This species is susceptible to infectious disease, which has an impact on human health through the farming of ducks and because of the important role of ducks in the ecology of the influenza A virus. The long-term objective of these proposed studies is to understand the immunogenetic basis of the duck's antibody response. Initial studies have shown that 2 of the genes encoding antibody heavy chain constant (C) regions in the duck (the alpha and upsilon genes) are in head-to-head orientation. The specific aims of the proposed work seek to answer the following questions. 1) Is the order of C region genes in the duck IgH locus (mu-alpha-upsilon) or (mu-upsilon- alpha)? Did the recombination events that produced the reorganization of the duck IgH locus result in the loss of the membrane exon associated with the alpha gene? 3) Is there a homolog of the delta gene present in the duck IgH locus? 4) In what manner does the head-to-head orientation of the upsilon and alpha genes affect the process of class switching to IgY or IgA in duck B cells? These questions will be approached through cloning and mapping of the duck IgH locus (by use of recombinant genomic phage and bacterial artificial chromosome libraries) and sequencing of critical regions of the locus. The nature of class-switching mechanisms will be investigated by the isolation and analysis of the circular DNA products of class switch recombination. The results of these proposed studies should provide insight into the manner in which specific aspects of C gene organization, such as head-to-head orientation, affect the functional expression of these genes, and add to our knowledge of the functional significance of different gene organizations found in the vertebrate IgH locus.

鸭子的免疫系统功能很差，被描述为无能。 该物种易感染传染病，通过养鸭和鸭在甲型流感病毒生态中的重要作用对人类健康产生影响。 这些拟议研究的长期目标是了解鸭的抗体反应的免疫遗传学基础。 最初的研究表明，鸭中编码抗体重链恒定（C）区的2个基因（α和upregulatory基因）是头对头定向的。 拟议工作的具体目标是设法回答下列问题。 1)鸭IgH基因座中C区基因的顺序是（μ-α-upper）还是（μ-upper-α）？ 鸭IgH基因座重组的重组事件是否导致与α基因相关的膜外显子丢失？ 3)在鸭IgH基因座中是否存在δ基因的同源物？ 4)在鸭B细胞中，upper和alpha基因的头对头方向以何种方式影响向IgY或伊加的类转换过程？ 这些问题将通过克隆和映射的鸭IgH基因座（通过使用重组基因组噬菌体和细菌人工染色体库）和基因座的关键区域的测序来解决。 类别转换机制的本质将通过分离和分析类别转换重组的环状DNA产物来研究。 这些拟议研究的结果应该可以深入了解C基因组织的特定方面（例如头对头方向）影响这些基因功能表达的方式，并增加我们对不同基因组织功能意义的了解在脊椎动物IgH基因座中发现。