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RABBIT ALLOTYPES--STRUCTURE, ORGANIZATION AND REGULATED EXPRESSION OF IG GENES

RABBIT ALLOTYPES--STRUCTURE, ORGANIZATION AND REGULATED EXPRESSION OF IG GENES
兔同种异型——IG 基因的结构、组织和调控表达
批准号:
4688404
负责人:
R G MAGE
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至

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中文摘要
翻译
我们试图从分子水平上解释该基因的表达缺失 Basilea兔体内通常存在k1-b9型kappa轻链。 未发现与Ckappa1相关的重大缺失或重排 南方分析。我们克隆并测定了Ckappa1基因及其3‘端和 5‘侧翼区,并在受体剪接中发现G到A的转变 Jkappa-Ckappa内含子的位置。不变量AG/到AA/的这种变化 为K1轻链表达缺失提供了分子解释。 我们克隆并测序了一只A3表型兔的VH基因。 试图了解血吸虫病血清学观察的分子基础 潜伏的VHA异型表达。我们发现兔子的VH基因 异常接近(大约相隔3kb)和编码的异常组合 与同种异型相关的密码子。现在看来,不太可能所有的兔子 具有相同的VH区结构基因的基因组含量或 VH同种异型的等位基因行为只是反映了调控基因。 由于同种异型相关位置上的大多数替代氨基酸可能是 通过单碱基变化、体细胞突变和/或 类似基因转换的事件可能至少解释了一些观察到的 潜伏VHA同种异型。兔VH基因的近似性可能会增强 类似基因转换的事件。 我们克隆并测序了两个胸腺来源的cdna克隆,这两个克隆编码 兔T细胞受体β链的恒定区和高表达 与人类和小鼠的序列同源。一个cdna编码一种不寻常的 CBeta的非VBeta序列5‘将产生未知的蛋白质 功能。另一个编码兔VBeta,与小鼠有72.5%的同源性 维贝塔。此外,对应的单拷贝基因组的序列 另一只兔子的VBeta具有相同的序列,表明没有 表达的VBeta基因发生了体细胞突变。
英文摘要
We sought a molecular explanation for the loss of expression of the normally predominant K1-b9 type of kappa light chains in Basilea rabbits. No major deletions or rearrangements associated with Ckappa1 were found by Southern analyses. We cloned and sequenced the Ckappa1 gene and its 3' and 5' flanking regions and found a G to A transition in the acceptor splice site of the Jkappa-Ckappa intron. This change in an invariant AG/ to AA/ provides a molecular explanation for the loss of K1 light chain expression. We cloned and sequenced VH genes from a rabbit of a3 phenotype in an attempt to understand the molecular basis for serological observations of latent VHa allotype expression. We found rabbit VH genes that were unusually close (approximately 3kb apart) and encoded unusual combinations of allotype-correlated codons. It now appears unlikely that all rabbits have the same genomic content of structural genes for VH regions or that the allelic behavior of VH allotypes simply reflects regulatory genes. Since most alternative amino acids at allotype-correlated positions can be derived from each other by single-base changes, somatic mutations and/or gene-conversion-like events may explain at least some observations of latent VHa allotypes. The proximity of rabbit VH genes may enhance gene-conversion-like events. We cloned and sequenced two thymus-derived cDNA clones that encode the constant region of the rabbit T cell receptor Beta chain and found high homology to the human and murine sequences. One cDNA encodes an unusual non-VBeta sequence 5' of CBeta that would produce a protein with unknown function. The other encodes a rabbit VBeta with 72.5% homology to a mouse VBeta. In addition, the sequence of a corresponding single-copy genomic VBeta from a second rabbit had an identical sequence suggesting that no somatic mutations have occurred in the expressed VBeta gene.
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RABBIT ALLOTYPES--STRUCTURE, ORGANIZATION AND REGULATED EXPRESSION OF IG GENES
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