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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
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中文摘要
翻译
我们试图从分子上解释, 在Basilea兔中正常占优势的K1-b 9型κ轻链。 未发现与Ckappa 1相关的重大缺失或重排。 南方分析 我们克隆并测序了Ckappa 1基因及其3'端和 5'侧翼区,并发现在受体剪接G到A的转换 Jkappa-Ckappa内含子的位置。 不变式AG/到AA/的这种变化 提供了K1轻链表达缺失的分子解释。 我们从一只a3表型的兔中克隆了VH基因并进行了序列测定。 试图了解血清学观察的分子基础, 潜在VHa同种异型表达。 我们发现兔子的VH基因 异常接近(约3 kb间隔)和编码的异常组合 同种异型相关密码子 现在看来所有的兔子 具有相同的VH区结构基因的基因组含量,或者 VH同种异型的等位基因行为仅仅反映了调节基因。 由于同种异型相关位置处的大多数替代氨基酸可以是 通过单碱基变化、体细胞突变和/或 类似基因转换的事件可以解释至少一些观察结果, 潜在VHa同种异型。 兔VH基因的接近可能会增强 类似基因转换的事件 我们克隆并测序了两个胸腺衍生的cDNA克隆, 兔T细胞受体β链的恒定区,并发现高 与人和鼠序列同源。 一个cDNA编码一个不寻常的 CBeta的5'端的非V β序列,其将产生具有未知的 功能 另一个编码兔VBeta基因,与小鼠的同源性为72.5 VBeta 此外,相应的单拷贝基因组的序列 来自第二只兔子的VBeta具有相同的序列,这表明没有 在表达的V β基因中发生了体细胞突变。
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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