ORGANIZATION OF IMMUNOGLOBULIN HEAVY-CHAIN GENES AND ALLELIC DELETION MODEL

ORGANIZATION OF IMMUNOGLOBULIN HEAVY-CHAIN GENES AND ALLELIC DELETION MODEL
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DOI:
10.1073/pnas.75.5.2140
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发表时间:
1978-01-01
影响因子:
11.1
通讯作者:
KATAOKA, T
KATAOKA, T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
HONJO, T;KATAOKA, T

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通过杂交动力学分析评估编码小鼠免疫球蛋白[Ig]重链恒定区γ1、γ2a和γ3的基因序列在小鼠基因组中出现的次数。在产生IgM或IgG3的正常组织和骨髓瘤中,所有这三个基因在每个单倍体基因组中各有一个拷贝。然而,产生IgG1的骨髓瘤,每个单倍体基因组包含1个拷贝的γ1和γ2a基因和0.5个拷贝的γ3基因。产生IgG2b的骨髓瘤每个单倍体基因组包含1个拷贝的γ2a基因和0.5个拷贝的γ1和γ3基因。产生IgG2a的骨髓瘤每个单倍体基因组包含1个拷贝的γ2a基因和0.5个拷贝的γ1和γ3基因。在骨髓瘤中产生IgA,全部为3伽马。基因在每个单倍体基因组中被呈现0.5次。为了解释这一结果,提出了一个等位基因缺失模型:重链恒定区基因的特异性缺失伴随着可变区基因到恒定区基因的重组;位于两个连接序列之间的染色体部分被从染色体上切除;重组发生在其中一个等位基因上。重链基因按以下顺序排列在1条染色体上:可变区基因、未知间隔区序列、γ1、γ3、γ1、γ2b、γ2a和α。
The number of times the gene sequence encoding constant regions of mouse immunoglobulin [Ig] heavy chains .gamma.1, .gamma.2a, and .gamma.3 are represented in the mouse genome was assessed by hybridization kinetic analysis. All 3 genes are present at 1 copy each per haploid genome in normal tissues and myelomas producing IgM or IgG3. IgG1-producing myelomas, however, contain 1 copy each of the .gamma.1 and .gamma.2a genes and 0.5 copy of the .gamma.3 gene per haploid genome. IgG2b-producing myelomas contain 1 copy of the .gamma.2a gene and 0.5 copy each of the .gamma.1 and .gamma.3 genes per haploid genome. IgG2a-producing myelomas contain 1 copy of the .gamma.2a gene and 0.5 copy each of the .gamma.1 and .gamma.3 genes per haploid genome. In myelomas producing IgA, all 3 .gamma. genes are represented 0.5 time per haploid genome. In order to account for the results an allelic deletion model is proposed: the specific deletion of heavy chain constant region genes accompanies the recombination of a variable region gene to a constant region gene; the portion of the chromosome that resides between 2 joining sequences is excised out of the chromosome; the recombination occurs on 1 of the alleles. Heavy chain genes are arranged on 1 chromosome in the following order; variable region genes, unknown spacer sequence, .mu., .gamma.3, .gamma.1, .gamma.2b, .gamma.2a and .alpha.