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兔免疫球蛋白κ轻链基因座3'端增强子序列的鉴定

Identification of enhancer sequences 3' of the rabbit Ig kappa L chain loci.

作者信息

Hole N J, Harindranath N, Young-Cooper G O, Garcia R, Mage R G

机构信息

Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.

出版信息

J Immunol. 1991 Jun 15;146(12):4377-84.

PMID:1904082
Abstract

The rabbit is useful for studies of Ig L chain gene expression because of a great disparity in expression of two isotypic forms of the kappa L chain. Normally, K1 is expressed at high levels and K2 is almost silent; expression of K2 increases in mutant or experimentally allotype-suppressed animals. The reasons for the preferential utilization of the K1 isotype have not been fully elucidated. We were interested in looking for second enhancers 3' of the C kappa genes because the absence of a 3' enhancer in the K2 locus could explain the preferential utilization of the K1 isotype. However, we found a strong region of enhancer activity about 7 kb downstream of the C kappa 2 gene. Sequences in this region are highly conserved between rabbit, man, and mouse. There also appears to be a homologous 3' enhancer region in the rabbit K1 locus. We also confirmed earlier reports that the rabbit K1 intron enhancer is inactive in transient transfections into mouse B cells but find that the same construct has low but significant activity in a human B cell line. In a comparable construct the K2 intron enhancer is without activity suggesting possible differential activity of the intronic enhancers.

摘要

兔子对于免疫球蛋白轻链基因表达的研究很有用,因为κ轻链的两种同种型形式在表达上存在很大差异。正常情况下,K1高水平表达而K2几乎不表达;在突变体或实验性同种异型抑制动物中,K2的表达增加。优先利用K1同种型的原因尚未完全阐明。我们有兴趣寻找κ基因下游3'端的第二个增强子,因为K2基因座中缺乏3'增强子可以解释K1同种型的优先利用。然而,我们在κ2基因下游约7 kb处发现了一个强增强子活性区域。该区域的序列在兔子、人类和小鼠之间高度保守。在兔子K1基因座中似乎也存在一个同源的3'增强子区域。我们还证实了早期的报道,即兔子K1内含子增强子在瞬时转染到小鼠B细胞中时无活性,但发现相同的构建体在人B细胞系中具有低但显著的活性。在一个类似的构建体中,K2内含子增强子无活性,提示内含子增强子可能存在差异活性。

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