DUCK ANTIBODY GENES--UNUSUAL ORGANIZATION AND EXPRESSION

这只鸭子的免疫系统功能很差，被描述为无能。由于鸭子在甲型流感病毒生态中的重要作用，这一物种容易感染传染病，通过养鸭对人类健康产生影响。这些拟议研究的长期目标是了解鸭子抗体反应的免疫遗传学基础。初步研究表明，在鸭体内编码抗体重链恒定(C)区的两个基因(α基因和upsilon基因)是头对头定向的。拟议工作的具体目标力求回答以下问题。1)鸭IgH基因座上C区基因的顺序是(Mu-α-upsilon)还是(Mu-α-upsilon)？引起鸭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的丢失？3)鸭IgH基因座中是否存在Delta基因的同源基因？4)上游基因和α基因的头对头方向如何影响鸭B细胞向IgY或IgA类的转换过程？这些问题将通过克隆和定位鸭IgH基因座(使用重组基因组噬菌体和细菌人工染色体文库)和对该基因座的关键区域进行测序来解决。通过分离和分析类交换重组的环状DNA产物来研究类交换机制的本质。这些拟议的研究结果将有助于深入了解C基因组织的特定方面，如头对头定向，如何影响这些基因的功能表达，并增加我们对脊椎动物IgH基因座中不同基因组织的功能意义的了解。

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.