Establishment of a Cre-rat resource for creating conditional and physiological relevant models of human diseases.
Establishment of a Cre-rat resource for creating conditional and physiological relevant models of human diseases.
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DOI：
10.1007/s11248-020-00226-7
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发表时间：
2021-03
影响因子：
3
通讯作者：
Chen-Tsai RY
中科院分区：
文献类型：
--
作者：
Zhang H;Zheng Q;Chen-Tsai RY
本研究的目的是建立Cre/loxP大鼠资源，用于人类疾病的条件和生理预测大鼠模型。实验大鼠（r.n norvegicus）是生物医学研究领域的中心实验动物，如心血管疾病、衰老、传染病、自身免疫、癌症模型、移植生物学、炎症、癌症风险评估、工业毒理学、药理学、行为和成瘾研究以及神经生物学。迄今为止，与小鼠相比，创造转基因大鼠的能力受到限制，主要原因是大鼠缺乏基因操作工具和技术。核酸酶的最新进展，如CRISPR/Cas9（聚集规律间隔的短回文重复序列/CRISPR相关蛋白9），以及TARGATT™整合酶系统，可以快速，高效和位点特异性地将外源遗传元件引入大鼠基因组。在这里，我们报告了使用targeatt™，CRISPR/Cas9和随机转基因方法产生组织特异性，可诱导的转基因Cre大鼠作为工具模型。更具体地说，我们通过Cre- ert2 /loxP系统生成了允许在时间和空间上控制基因表达或敲除的Cre驱动大鼠模型（条件模型）。共生成10个Cre大鼠系和1个Cre报告/测试系，包括8个神经特异性Cre表达系和2个心血管特异性Cre表达系。所有这些细胞系均已存入大鼠资源和研究中心，为利用大鼠模型进行人类疾病研究的生物医学界提供了急需的资源。
The goal of this study is to establish a Cre/loxP rat resource for conditional and physiologically predictive rat models of human diseases. The laboratory rat (R. norvegicus) is a central experimental animal in several fields of biomedical research, such as cardiovascular diseases, aging, infectious diseases, autoimmunity, cancer models, transplantation biology, inflammation, cancer risk assessment, industrial toxicology, pharmacology, behavioral and addiction studies, and neurobiology. Up till recently, the ability of creating genetically modified rats has been limited compared to that in the mouse mainly due to lack of genetic manipulation tools and technologies in the rat. Recent advances in nucleases, such as CRISPR/Cas9 (clustered regularly-interspaced short palindromic repeats/CRISPR associated protein 9), as well as TARGATT™ integrase system enables fast, efficient and site-specific introduction of exogenous genetic elements into the rat genome. Here, we report the generation of a collection of tissue-specific, inducible transgenic Cre rats as tool models using TARGATT™, CRISPR/Cas9 and random transgenic approach. More specifically, we generated Cre driver rat models that allow controlled gene expression or knockout (conditional models) both temporally and spatially through the Cre-ERT2/loxP system. A total of 10 Cre rat lines and one Cre reporter/test line were generated, including eight (8) Cre lines for neural specific and two (2) lines for cardiovascular specific Cre expression. All of these lines have been deposited with the Rat Resource and Research Center and provide a much-needed resource for the bio-medical community who employ rat models for their studies of human diseases.
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影响因子：
30.8
作者：
Guenther CA;Tasic B;Luo L;Bedell MA;Kingsley DM
通讯作者：
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影响因子：
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作者：
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DOI：
10.1006/bbrc.1997.7124
发表时间：
1997-08-28
影响因子：
3.1
作者：
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通讯作者：
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DOI：
10.1073/pnas.1121203109
发表时间：
2012-06-12
影响因子：
11.1
作者：
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通讯作者：
Kuehn, Ralf
DOI：
10.1073/pnas.1009424107
发表时间：
2010-08-24
影响因子：
11.1
作者：
Meyer, Melanie;de Angelis, Martin Hrabe;Kuehn, Ralf
通讯作者：
Kuehn, Ralf