Generation of a Fanconi anemia models in the pig by advanced genome engineering

通过先进的基因组工程在猪中生成范可尼贫血模型

• 批准号: 192206558
• 负责人: Professor Dr. Zoltan Ivics
• 金额: --
• 依托单位: Institut für Nutztiergenetik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/192206558?language=en
• 关键词: Generation; Fanconi; anemia; models; pig

In the previous DFG-funded project Transposon-mediated transgenesis in the pig genome a highly efficient approach for germline transgenesis coupled with reliable transgene expression in the pig was established employing the SB transposon system. Here, we propose to establish an efficient in ovo genome engineering approach in the pig model by employing transposon, Cre/loxP and clustered regulated interspaced short palindromic repeat (CRISPR/Cas9) systems. The proposed experiments will exploit the transposon-transgenic animals established in the previous funding period to provide proof of principle for single step engineering of the pig genome with the aim to generate a pig disease model for Fanconi anemia. The available mouse models for Fanconi anemia do not recapitulate certain features of the disease. It is anticipated that a Fanconi pig will mirror the disease phenotype seen in humans and will become an important model for the development of curative therapies. The proposed project is based on previous own expertise in establishing transposon transgenesis, as well as generation of induced pluripotent stem cells in rodents and pigs.

在之前DFG资助的转座子介导的猪基因组转基因项目中，采用SB转座子系统建立了一种高效的生殖系转基因方法，并在猪中进行可靠的转基因表达。在这里，我们建议通过使用转座子、Cre/loxP和成簇调节间隔短回文重复序列（CRISPR/Cas9）系统在猪模型中建立有效的卵内基因组工程方法。拟议的实验将利用上一个资助期建立的转座子转基因动物，为猪基因组的单步工程提供原理证明，目的是生成范可尼贫血的猪疾病模型。现有的范可尼贫血小鼠模型不能概括该疾病的某些特征。预计Fanconi猪将反映在人类中观察到的疾病表型，并将成为开发治愈性疗法的重要模型。拟议的项目是基于以前自己在建立转座子转基因方面的专业知识，以及在啮齿动物和猪中产生诱导多能干细胞。

项目成果

Identification and re-addressing of a transcriptionally permissive locus in the porcine genome

猪基因组中转录允许位点的鉴定和重新寻址

• DOI: 10.1007/s11248-015-9914-4
• 发表时间: 2016
• 期刊: Transgenic Research
• 影响因子: 3
• 作者: Garrels W;Mukherjee A;Holler S;Cleve N;Talluri TR;Barg-Kues B;Diederich M;Köhler P;Diederich M;Petersen B;Lucas-Hahn;Niemann H;Izsvac Z;Ivics Z;Kues WA
• 通讯作者: Kues WA

Cytoplasmic injection of murine zygotes with Sleeping Beauty transposon plasmids and minicircles results in the efficient generation of germline transgenic mice

• DOI: 10.1002/biot.201500218
• 发表时间: 2016-01-01
• 期刊: BIOTECHNOLOGY JOURNAL
• 影响因子: 4.7
• 作者: Garrels, Wiebke;Talluri, Thirumala R.;Kues, Wilfried A.
• 通讯作者: Kues, Wilfried A.