The main mission of our core is to assist NIH scientists in generating genetically engineered animal models to support their scientific research. Genome engineering technologies have been advancing very rapidly in the past decade, especially the so-called CRISPR (clustered regularly interspaced short palindromic repeat) method has dramatically changed the way animal models are created. In the past several years, our core has spent a significant portion of our efforts on keeping up with the latest technological developments and efficiently applying them to animal model generation. We have been collaborating with Dr. Lothar Hennighausens laboratory on developing capabilities for using base-editors, a latest variant of CRISPR technology, to generate knockin mouse lines, and using whole genome sequencing approaches to analyze on-target and off-target mutations caused by various base-editors as well as the conventional CRISPR/Cas9 method. We have also successfully used Cpf1, an alternative enzyme to Cas9, to generate mouse models. Besides developing capabilities in using the latest CRISPR technology, we have been continuingly using the classical genetic engineering, embryonic stem cell, and assisted reproductive technologies to provide a range of services, including generating transgenic mice and chimeric mice, re-deriving mouse lines, resurrecting mouse lines using in vitro fertilization, and assessing stem cell differentiation propensities through teratoma formation assay. Overall, these collaborations and technical services have led to over 20 co-authored publications. In addition, Dr. Yubin Du, a biologist working in our core, and I have co-edited a volume of Methods in Molecular Biology, which consisted 30 chapters of modern methods related to animal model development.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICHL005907-12
Application #
10023855
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2019
Total Cost
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
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State
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Zip Code
Deis, Jessica A; Guo, Hong; Wu, Yingjie et al. (2018) Lipocalin 2 regulates retinoic acid-induced activation of beige adipocytes. J Mol Endocrinol :
Lin, Yongshun; Liu, Huimin; Klein, Michael et al. (2018) Efficient differentiation of cardiomyocytes and generation of calcium-sensor reporter lines from nonhuman primate iPSCs. Sci Rep 8:5907
Zhang, Yingfan; Liu, Chengyu; Adelstein, Robert S et al. (2018) Replacing nonmuscle myosin 2A with myosin 2C1 permits gastrulation but not placenta vascular development in mice. Mol Biol Cell 29:2326-2335
Jiao, Delong; Cai, Zhenyu; Choksi, Swati et al. (2018) Necroptosis of tumor cells leads to tumor necrosis and promotes tumor metastasis. Cell Res 28:868-870
Zhuang, Lenan; Jang, Younghoon; Park, Young-Kwon et al. (2018) Depletion of Nsd2-mediated histone H3K36 methylation impairs adipose tissue development and function. Nat Commun 9:1796
Xing, Shaojun; Shao, Peng; Li, Fengyin et al. (2018) Tle corepressors are differentially partitioned to instruct CD8+ T cell lineage choice and identity. J Exp Med 215:2211-2226
Liu, Tanbin; Hu, Yi; Guo, Shiyin et al. (2018) Identification and characterization of MYH9 locus for high efficient gene knock-in and stable expression in mouse embryonic stem cells. PLoS One 13:e0192641
Vizcardo, Raul; Klemen, Nicholas D; Islam, S M Rafiqul et al. (2018) Generation of Tumor Antigen-Specific iPSC-Derived Thymic Emigrants Using a 3D Thymic Culture System. Cell Rep 22:3175-3190
Pan, Haihui; Yan, Ye; Liu, Chengyu et al. (2017) The role of ZKSCAN3 in the transcriptional regulation of autophagy. Autophagy 13:1235-1238
Shin, Ha Youn; Wang, Chaochen; Lee, Hye Kyung et al. (2017) CRISPR/Cas9 targeting events cause complex deletions and insertions at 17 sites in the mouse genome. Nat Commun 8:15464

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