Transgenes of the mouse immunoglobulin heavy chain locus, lacking distal elements in the 3' regulatory region, are impaired for class switch recombination.
Transgenes of the mouse immunoglobulin heavy chain locus, lacking distal elements in the 3' regulatory region, are impaired for class switch recombination.
复制标题
DOI：
10.1371/journal.pone.0055842
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Collins JT
中科院分区：
文献类型：
--
作者：
Dunnick WA;Shi J;Fontaine C;Collins JT
免疫球蛋白重（H）链类别转换由μ和γ、α或ε恒定区基因之间的缺失重组事件介导。这种重组事件在免疫应答期间通过位于恒定区基因3′的调节区上调。我们研究开关重组使用整个鼠H链恒定区基因座的转基因。我们分离了两种小鼠品系，其中H链转基因在其3′端被截短。两个转基因株系中的截短导致3′端增强子（HS4）和具有绝缘子样结构和活性的区域的缺失。尽管两种截短的转基因都能很好地表达µ H链基因，但它们与转基因γ和α恒定区基因的转换重组非常低或检测不到。对于这两种转基因株系，一些H链恒定区基因的种系转录严重受损。然而，对于具有较大截短的转基因系，γ1和γ2a基因的生殖系转录处于野生型水平，而对于具有较小截短的转基因系，γ1和γ2a基因的生殖系转录处于降低的水平。所有H链基因的类别转换重组的急剧减少和一些H链基因的种系转录的不同减少可能是由（i）插入位点效应或（ii）类别转换重组和转录的增强子元件缺失或（iii）两种效应的组合引起的。
The immunoglobulin heavy (H) chain class switch is mediated by a deletional recombination event between µ and γ, α, or ε constant region genes. This recombination event is upregulated during immune responses by a regulatory region that lies 3′ of the constant region genes. We study switch recombination using a transgene of the entire murine H chain constant region locus. We isolated two lines of mice in which the H chain transgenes were truncated at their 3′ ends. The truncation in both transgenic lines results in deletion of the 3′-most enhancer (HS4) and a region with insulator-like structure and activities. Even though both truncated transgenes express the µ H chain gene well, they undergo very low or undetectable switch recombination to transgenic γ and α constant region genes. For both transgenic lines, germline transcription of some H chain constant regions genes is severely impaired. However, the germline transcription of the γ1 and γ2a genes is at wild type levels for the transgenic line with the larger truncation, but at reduced levels for the transgenic line with the smaller truncation. The dramatic reduction in class switch recombination for all H chain genes and the varied reduction in germline transcription for some H chain genes could be caused by (i) insertion site effects or (ii) deletion of enhancer elements for class switch recombination and transcription, or (iii) a combination of both effects.
登录
查看更多内容
影响因子：
4.4
作者：
Degner, Stephanie C.;Wong, Timothy P.;Jankevicius, Gytis;Feeney, Ann J.
通讯作者：
Feeney, Ann J.
影响因子：
5.3
作者：
Garrett, FE;Emelyanov, AV;Birshtein, BK
通讯作者：
Birshtein, BK
影响因子：
15.3
作者：
GIUSTI, AM;MANSER, T
通讯作者：
MANSER, T
影响因子：
14.9
作者：
LIEBERSON, R;GIANNINI, SL;ECKHARDT, LA
通讯作者：
ECKHARDT, LA
影响因子：
4.4
作者：
Dunnick，Wesley A.;Shi，Jian;Collins，John T.
通讯作者：
Collins，John T.