Generation and characterization of CD19-iCre mice as a tool for efficient and specific conditional gene targeting in B cells.
Generation and characterization of CD19-iCre mice as a tool for efficient and specific conditional gene targeting in B cells.
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DOI：
10.1038/s41598-021-84786-6
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发表时间：
2021-03-09
影响因子：
4.6
通讯作者：
Baba Y
中科院分区：
文献类型：
--
作者：
Yasuda T;Saito Y;Ono C;Kawata K;Baba A;Baba Y
Cre/loxP系统是产生条件性基因敲除(KO)小鼠和阐明体内基因功能的有力工具。CD19-Cre和Mb1-iCre转基因小鼠通常用于建立B细胞特异性KO小鼠，并研究B细胞的发育及其生理和病理生理作用。然而，CD19-Cre品系的低效率和Mb1-iCre品系偶尔的异位重组给它们的使用带来了挑战。因此，我们开发了一种CD19密码子改进的Cre(CD19-iCre)敲入小鼠，将T2a-iCre序列插入CD19基因座，恰好在停止密码子之前。CD19-iCre小鼠与现有模型比较，与rosa26-EYFP报告小鼠杂交，评估它们在携带不同Cre等位基因的B细胞上的重组活性。与CD19-Cre小鼠相比，CD19-Cre小鼠在B细胞发育的早期阶段表现出更有效的Cre重组。CD19-iCre和Mb1-iCre的效率相似，但CD19-iCre的B系特异性重组更为严格。此外，CD19-Cre模型的实用价值优于CD19-Cre小鼠在IL10-FLOX小鼠中的缺失效率。因此，CD19-iCre系是针对B细胞室的高效基因靶向的有价值的工具。
The Cre/loxP system is a powerful tool for generating conditional gene knockout (KO) mice and elucidate gene function in vivo. CD19-Cre and Mb1-iCre transgenic mice are commonly used for generating B cell-specific KO mice and investigate the development, as well as the physiological and pathophysiological roles of B cells. However, the CD19-Cre line low efficiency and the Mb1-iCre line occasional ectopic recombination represent challenges for their use. Thus, we developed a CD19-codon-improved Cre (CD19-iCre) knock-in mouse with the T2A-iCre sequence inserted into the Cd19 locus, just before the stop codon. The CD19-iCre mice were compared with existing models, crossed with the Rosa26-EYFP reporter mice, and their recombination activity in B cells carrying different Cre alleles was assessed. CD19-iCre mice showed more effective Cre recombination in the early B cell developmental stages compared with the CD19-Cre mice. The efficiencies of the CD19-iCre and Mb1-iCre lines were similar; however, the B lineage-specific recombination was more stringent in the CD19-iCre line. Furthermore, the utility value of the CD19-iCre model was superior than that of the CD19-Cre mice regarding deletion efficiency in IL10-floxed mice. Thus, the CD19-iCre line is a valuable tool for highly efficient gene targeting specific to the B cell compartment.
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DOI：
10.1016/j.tig.2017.12.008
发表时间：
2018-05
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
Song AJ;Palmiter RD
通讯作者：
Palmiter RD
DOI：
10.1038/nri.2017.24
发表时间：
2017-07
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Rawlings DJ;Metzler G;Wray-Dutra M;Jackson SW
通讯作者：
Jackson SW
影响因子：
14.9
作者：
Rickert, RC;Roes, J;Rajewsky, K
通讯作者：
Rajewsky, K
DOI：
10.1073/pnas.0605944103
发表时间：
2006-09-12
影响因子：
11.1
作者：
Hobeika, E.;Thiemann, S.;Reth, M.
通讯作者：
Reth, M.
影响因子：
1.5
作者：
Shimshek, DR;Kim, J;Sprengel, R
通讯作者：
Sprengel, R