IG GENETICS--ONTOGENY AND DIFFERENTIATION OF CELLS OF THE RABBIT IMMUNE SYSTEM

IG遗传学--兔免疫系统细胞的个体发育和分化

• 批准号: 3803078
• 负责人: R G MAGE
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3803078
• 关键词: RNA splicing; T cell receptor; cell differentiation; developmental genetics; gender difference; gene deletion mutation; gene expression; genetic manipulation; genetic mapping; genetic recombination; genetic regulation; genetic strain; immunoglobulin genes; laboratory rabbit; leukocyte activation /transformation; lymphocyte; mutant; nucleic acid sequence; phenotype; pseudogenes; species difference

We use techniques of classical immunogenetics and of molecular biology to study the genetics of rabbit immunoglobulins (Igs) and T cell receptors (Tcr) and to investigate the regulated expression of Ig and Tcr genes during lymphoid cell development. We reported the thirteenth laboratory observation of a VH-CH recombination (R2M) in the rabbit. All thirteen recombinations have occurred in the male parent. The R2M recombination site maps 3'of the VH genes and 5'of the JH genes as did the sites of three previously characterized recombinations. The R2M site maps 3'of the D1d DH gene which is toward the 3'end of the DH-containing region and is probably in or near stretches of repetitive DNA. There may be two or more "hot-spots of recombination" within or near stretches of repetitive DNA in the DH-containing region of the rabbit. We obtained the complete genomic sequences of the DBeta2 and JBeta2 segments associated with a chimeric CBeta gene present in some rabbits. The rabbit JBeta2 cluster has six functional segments, one pseudogene, and a remnant of another pseudogene between JBeta2.2 and JBeta2.3, equivalent to the one found in man at the same location. The JBeta2.5 gene segment of rabbit has lost the splice signal and is a pseudogene unlike its counterparts in man and mouse. The general organization of the gene segments in the DBeta2-JBeta2 regions of all three species is remarkably conserved over long stretches of DNA sequence; there is higher similarity to human than mouse. Rabbits were bred at the NIH to produce elevated levels of lambda light chains lacking c2l and expressing only c7. These rabbits were shown to produce mRNA and proteins with sequences corresponding to the products of a previously identified genomic lambda light chain gene, Clambda6. The production of c2l is known to be due to expression of Clambda5. The c2l-negative phenotype reflects deletion of a region including Jlambda5. Tbe c7-negative phenotype also appears to result from a deletion.

我们使用经典免疫遗传学和分子生物学技术 研究兔免疫球蛋白（IGS）和T细胞的遗传学 受体（TCR），并研究Ig和 淋巴样细胞发育过程中的TCR基因。 我们报道了VH-CH的第十三实验室观察 兔子中的重组（R2M）。所有13个重组都有 发生在男性父母中。 R2M重组站点地图3' VH基因和JH基因的5'和以前的三个位点一样 重组的特征。 D1D DH基因的R2M站点地图3'' 这是朝着含DH区域的3'End的3'End 或接近重复的DNA。 可能有两个或更多 重复性DNA内或附近的“重组热点” 在兔子的DH区域。 我们获得了DBETA2和JBETA2的完整基因组序列 与某些兔子中存在的嵌合CBETA基因相关的片段。 Rabbit JBETA2群集具有六个功能性段，一个伪代码， 以及JBETA2.2和JBETA2.3之间的另一个伪代的残余物， 相当于在同一位置中发现的人。 jbeta2.5 兔子的基因片段失去了剪接信号，是假基因 与男人和鼠标中的对应物不同。 一般组织 这三个物种的DBETA2-JBETA2区域中的基因段是 在长长的DNA序列中明显保守；有 与人类相似的相似性比小鼠更高。 兔子在NIH上繁殖以产生升高的兰伯达光 缺乏C2L并仅表示C7的链。 这些兔子被证明 产生mRNA和蛋白质，其序列与产品相对应 先前鉴定的基因组Lambda轻链基因Clambda6。 C2L的产生归因于Clambda5的表达。 这 C2L阴性表型反映了包括Jlambda5在内的区域的缺失。 TBE C7阴性表型也似乎是由缺失引起的。