Genetic Removal of the CH1 Exon Enables the Production of Heavy Chain-Only IgG in Mice.
Genetic Removal of the CH1 Exon Enables the Production of Heavy Chain-Only IgG in Mice.
复制标题
CH1 外显子的基因去除使得小鼠能够产生纯重链 IgG
DOI：
10.3389/fimmu.2018.02202
复制
发表时间：
2018
影响因子：
7.3
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Zhang T;Cheng X;Yu D;Lin F;Hou N;Cheng X;Hao S;Wei J;Ma L;Fu Y;Ma Y;Ren L;Han H;Yu S;Yang X;Zhao Y
纳米抗体在许多领域具有巨大的应用潜力。然而，它们自然来源于仅有重链的抗体(HcAbbs)，这种抗体缺乏轻链和CH1结构域，只在骆驼和鲨鱼中发现。在这项研究中，我们研究了γ1基因CH1外显子的精确遗传去除是否能够在小鼠中产生功能上只有重链的IgG1.在转基因小鼠的血清中检测到缺少相关轻链的IgG1重链二聚体。然而，基因修饰导致IgG1的表达降低，而其他免疫球蛋白亚类的表达增加。与野生型小鼠相比，转基因小鼠对特定抗原的免疫反应较弱。用噬菌体展示的方法，可以从小鼠中筛选出抗原特异性的单区VH抗体，但其抗原结合亲和力比传统的单抗弱得多。尽管这一策略只取得了部分成功，但这项研究证实了在小鼠身上进行适当的基因修饰来生产理想的纳米体的可行性。
Nano-antibodies possess great potential in many applications. However, they are naturally derived from heavy chain-only antibodies (HcAbs), which lack light chains and the CH1 domain, and are only found in camelids and sharks. In this study, we investigated whether the precise genetic removal of the CH1 exon of the γ1 gene enabled the production of a functional heavy chain-only IgG1 in mice. IgG1 heavy chain dimers lacking associated light chains were detected in the sera of the genetically modified mice. However, the genetic modification led to decreased expression of IgG1 but increased expression of other IgG subclasses. The genetically modified mice showed a weaker immune response to specific antigens compared with wild type mice. Using a phage-display approach, antigen-specific, single domain VH antibodies could be screened from the mice but exhibited much weaker antigen binding affinity than the conventional monoclonal antibodies. Although the strategy was only partially successful, this study confirms the feasibility of producing desirable nano-bodies with appropriate genetic modifications in mice.
登录
查看更多内容
影响因子：
16
作者：
Feige, Matthias J.;Groscurth, Sandra;Marcinowski, Moritz;Shimizu, Yuichiro;Kessler, Horst;Hendershot, Linda M.;Buchner, Johannes
通讯作者：
Buchner, Johannes
DOI：
10.1038/nrg2703
发表时间：
2010-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
100.3
作者：
Beck, Alain;Wurch, Thierry;Corvaia, Nathalie
通讯作者：
Corvaia, Nathalie
影响因子：
64.8
作者：
HAAS, IG;WABL, M
通讯作者：
WABL, M
影响因子：
6.8
作者：
Koide, Shohei
通讯作者：
Koide, Shohei