DUCK ANTIBODY GENES--UNUSUAL ORGANIZATION AND EXPRESSION

鸭子的免疫系统功能很差，被形容为无能。这一物种易患传染病，通过养鸭和由于鸭在甲型流感病毒生态中的重要作用而对人类健康产生影响。这些拟议研究的长期目标是了解鸭抗体反应的免疫遗传学基础。初步研究表明，鸭体内2个编码抗体重链常数(C)区的基因（α和upsilon基因）是头对头定向的。拟议工作的具体目标是试图回答下列问题。1)鸭IgH位点C区基因的顺序是（mu- α -upsilon）还是（mu-upsilon- α）？产生鸭IgH位点重组的重组事件是否导致了与α基因相关的膜外显子的丢失？3)鸭的IgH位点是否存在delta基因的同源物？4)在鸭B细胞中，upsilon和α基因的头对头的方向如何影响类别转换到IgY或IgA的过程？这些问题将通过鸭IgH基因座的克隆和定位（利用重组基因组噬菌体和细菌人工染色体文库）以及基因座关键区域的测序来解决。类转换机制的性质将通过类转换重组的环状DNA产物的分离和分析来研究。这些拟议研究的结果将提供对C基因组织的特定方面，如头对头定向，影响这些基因功能表达的方式的见解，并增加我们对脊椎动物IgH位点中发现的不同基因组织的功能意义的认识。

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.