• Site-Specific Knockin Technology TARGATT™
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    • Long DNA Insertion
    Site-Specific Knockin Technology TARGATT™

TARGATT™ Cre-Rat

These transgenic Cre rat models have been developed using either ASC's proprietary integrase-based TARGATT™ System or CRISPR/Cas9 genome editing technology. These Cre rat lines can enable the development of physiologically relevant human cardiovascular, neurological diseases and other disease specific models.

These products were supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R44GM108071. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Applied StemCell, Inc. (ASC) announces that as of July 1, 2020, customers can order the Cre rat lines for research and industrial applications, through our partnering with the Rat Resource & Research Center (RRRC). For more questions regarding the Cre rat models, please visit the RRRC website at www.rrrc.us or contact the RRRC customer service email at rrrc@missouri.edu.

These strains will be available as:

 

RRRC#

Strain Name

868

Wnt1-CreERT2

869 

PDGFb-CreERT2 

870 

MOR23-CreERT2 

872 

HB9-CreERT2 

873 

Drd1a-CreERT2 

874 

Gad67-CreERT2  

876 

GFAP-CreERT2 

877 

Tie2-CreERT2  

878 

SMHC-CreERT2  

879

CAG-LSL-GFP-LacZ

Products and Services
Support Materials
Technical Details

Tissue/Cell-specificity

Rat line

Promoter

Reference

Developing neural crest and midbrain

Wnt1-CreERT2

1.3-kb 5' promoter and 5.5 kb 3' enhancer of the mouse Wnt1, wingless-related MMTV integration site 1

Chou et al 2013

Neurons of cortex, cerebellum, brain stem, spinal cord and olfactory bulb

PDGF-CreERT2

1.425-kb (-1360 to +75 relative to transcription start site) of the human PDGF B-chain gene

Sasahara et al 1991

Olfactory sensory neuronal lineage

MOR23-CreERT2

2.2-kb of mouse MOR23 promoter

Li et al 2004

Vassalli et al 2002

Neurons involved in the control of food intake (arcuate nucleus (hypothalamus) and solitary tract nucleus (hindbrain))

Pomc-CreERT2

13-kb of 5′ and 2 kb of 3′ mouse Pomc flanking sequences

 

Padilla et al 2011

Young et al 1998

Motor neurons

HB9-CreERT2

9-kb HB9 promoter

Arber et al 1999 Yang et al 2001; Nakano et al 2005; Tasic et al 2011

Dopamine D1 receptor-expressing neurons

Drd1a-CreERT2

8-kb mouse Drd1 promoter

 

Zhang et al 2006

GABAergic neurons, islet cells and spermatocytes

GAD67-CreERT2

 

10.2-kb containing 8.4-kb promoter and noncoding exon 0A and 0B of mouse glutamate decarboxylase 67

Kabayashi et al 2003

Rasmussen et al 2007

Glutamatergic neurons

PAG-CreERT2

2.4-kb rat PAG (phosphate-activated glutamase) promoter

Rasmussen et al 2007

Astrocytes in CNS

GFAP-CreERT2

2.2-kb human GFAP (glial fibrillary acidic protein)

Brenner et al 1994

Vascular endothelial cells including brain and retinal capillary

Tie2-CreERT2

2.1-kb promoter +1.7kb intron 1 enhancer of mouse Tie2 (vascular endothelial-specific receptor tyrosine kinase)

Schlaeger et al 1997

Ohtsuki et al 2005

Vascular smooth muscle cells

SMHC-CreERT2

2.3-kb rabbit smooth muscle myosin heavy chain promoter

Franz et al 1999

Cre reporter/test line expressing GFP and lacZ

CA-LoxP-STOP-LoxP-GFP-LacZ

1.7-kb CA (CMV-beta-actin) promoter

Tasic et al 2011

www.appliedstemcell.com

Publications

Book Chapters

Master Cell Line

  • Chi, X., Zheng, Q., Jiang, R., Chen-Tsai, R. Y., & Kong, L. J. (2019). A system for site-specific integration of transgenes in mammalian cells. PLOS ONE14(7), e0219842.

Description of the technology

  • Zhu, F., Gamboa, M., Farruggio, A. P., Hippenmeyer, S., Tasic, B., Schüle, B., … Calos, M. P. (2014). DICE, an efficient system for iterative genomic editing in human pluripotent stem cells. Nucleic Acids Research42(5), e34. http://doi.org/10.1093/nar/gkt1290.
  • Tasic, B., Hippenmeyer, S., Wang, C., Gamboa, M., Zong, H., Chen-Tsai, Y., & Luo, L. (2011). Site-specific integrase-mediated transgenesis in mice via pronuclear injection. Proceedings of the National Academy of Sciences of the United States of America108(19), 7902–7907. http://doi.org/10.1073/pnas.1019507108.

Commentary, comparison with other transgenic methods

  • Rossant, J., Nutter, L. M., & Gertsenstein, M. (2011). Engineering the embryo. Proceedings of the National Academy of Sciences108(19), 7659-7660.

Tet inducible mice generated by TARGATT™

Advantage of Hipp11 (H11) locus


Applications for mice generated by TARGATT™ (and cited/published articles)

  • Lindtner, S., Catta-Preta, R., Tian, H., Su-Feher, L., Price, J. D., Dickel, D. E., ... & Pennacchio, L. A. (2019). Genomic Resolution of DLX-Orchestrated Transcriptional Circuits Driving Development of Forebrain GABAergic Neurons. Cell reports, 28(8), 2048-2063.
  • Wang, T. A., Teo, C. F., Åkerblom, M., Chen, C., Tynan-La Fontaine, M., Greiner, V. J., ... & Jan, L. Y. (2019). Thermoregulation via Temperature-Dependent PGD2 Production in Mouse Preoptic Area. Neuron, 103(2), 309-322.
  • Clarke, B. A., Majumder, S., Zhu, H., Lee, Y. T., Kono, M., Li, C., ... & Byrnes, C. (2019). The Ormdl genes regulate the sphingolipid synthesis pathway to ensure proper myelination and neurologic function in mice. eLife8.
  • Carlson, H. L., & Stadler, H. S. (2019). Development and functional characterization of a lncRNA‐HIT conditional loss of function allele. genesis, e23351.
  • Chande, S., Ho, B., Fetene, J., & Bergwitz, C. (2019). Transgenic mouse model for conditional expression of influenza hemagglutinin-tagged human SLC20A1/PIT1. PloS one14(10), e0223052. doi:10.1371/journal.pone.0223052
  • Hu, Q., Ye, Y., Chan, L. C., Li, Y., Liang, K., Lin, A., ... & Pan, Y. (2019). Oncogenic lncRNA downregulates cancer cell antigen presentation and intrinsic tumor suppression. Nature immunology, 1.
  • Matharu, N., Rattanasopha, S., Tamura, S., Maliskova, L., Wang, Y., Bernard, A., ... & Ahituv, N. (2018). CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency. Science, eaau0629.
  • Barrett, R. D., Laurent, S., Mallarino, R., Pfeifer, S. P., Xu, C. C., Foll, M., ... & Hoekstra, H. E. (2018). The fitness consequences of genetic variation in wild populations of mice. bioRxiv, 383240.
  • Ibrahim, L. A., Huang, J. J., Wang, S. Z., Kim, Y. J., Li, I., & Huizhong, W. (2018). Sparse Labeling and Neural Tracing in Brain Circuits by STARS Strategy: Revealing Morphological Development of Type II Spiral Ganglion Neurons. Cerebral Cortex, 1-14.
  • Kumar, A., Dhar, S., Campanelli, G., Butt, N. A., Schallheim, J. M., Gomez, C. R., & Levenson, A. S. (2018). MTA 1 drives malignant progression and bone metastasis in prostate cancer. Molecular oncology.
  • Jang, Y., Wang, C., Broun, A., Park, Y. K., Zhuang, L., Lee, J. E., ... & Ge, K. (2018). H3. 3K4M destabilizes enhancer epigenomic writers MLL3/4 and impairs adipose tissue development. bioRxiv, 301986. doi:https://doi.org/10.1101/301986
  • Tang, Y., Kwon, H., Neel, B. A., Kasher-Meron, M., Pessin, J., Yamada, E., & Pessin, J. E. (2018). The fructose-2, 6-bisphosphatase TIGAR suppresses NF-κB signaling by directly inhibiting the linear ubiquitin assembly complex LUBAC. Journal of Biological Chemistry, jbc-RA118.
  • Chen, M., Geoffroy, C. G., Meves, J. M., Narang, A., Li, Y., Nguyen, M. T., ... & Elzière, L. (2018). Leucine Zipper-Bearing Kinase Is a Critical Regulator of Astrocyte Reactivity in the Adult Mammalian CNS. Cell Reports22(13), 3587-3597.
  • Kido, T., Sun, Z., & Lau, Y.-F. C. (2017). Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice. Scientific Reports7, 4113. http://doi.org/10.1038/s41598-017-04117-6.
  • Nouri, N., & Awatramani, R. (2017). A novel floor plate boundary defined by adjacent En1 and Dbx1 microdomains distinguishes midbrain dopamine and hypothalamic neurons. Development144(5), 916-927.
  • Li, K., Wang, F., Cao, W. B., Lv, X. X., Hua, F., Cui, B., ... & Yu, J. M. (2017). TRIB3 Promotes APL Progression through Stabilization of the Oncoprotein PML-RARα and Inhibition of p53-Mediated Senescence. Cancer Cell31(5), 697-710.
  • Matharu, N., Rattanasopha, S., Maliskova, L., Wang, Y., Hardin, A., Vaisse, C., & Ahituv, N. (2017). Promoter or Enhancer Activation by CRISPRa Rescues Haploinsufficiency Caused Obesity. bioRxiv, 140426.
  • Jiang, T., Kindt, K., & Wu, D. K. (2017). Transcription factor Emx2 controls stereociliary bundle orientation of sensory hair cells. eLife, 6, e23661.
  • Booze, M. L., Hansen, J. M., & Vitiello, P. F. (2016). A Novel Mouse Model for the Identification of Thioredoxin-1 Protein Interactions. Free Radical Biology & Medicine99, 533–543. http://doi.org/10.1016/j.freeradbiomed.2016.09.013.
  • Feng, D., Dai, S., Liu, F., Ohtake, Y., Zhou, Z., Wang, H., ... & Hayat, U. (2016). Cre-inducible human CD59 mediates rapid cell ablation after intermedilysin administration. The Journal of clinical investigation126(6), 2321-2333.
  • Sun, N., Yun, J., Liu, J., Malide, D., Liu, C., Rovira, I. I., … Finkel, T. (2015). Measuring in vivo mitophagy. Molecular Cell60(4), 685–696. http://doi.org/10.1016/j.molcel.2015.10.009.
  • Devine, W. P., Wythe, J. D., George, M., Koshiba-Takeuchi, K., & Bruneau, B. G. (2014). Early patterning and specification of cardiac progenitors in gastrulating mesoderm. eLife3, e03848. http://doi.org/10.7554/eLife.03848.
  • Fogg, P. C. M., Colloms, S., Rosser, S., Stark, M., & Smith, M. C. M. (2014). New Applications for Phage Integrases. Journal of Molecular Biology426(15), 2703–2716. http://doi.org/10.1016/j.jmb.2014.05.014.
  • Chen-Tsai, R. Y., Jiang, R., Zhuang, L., Wu, J., Li, L., & Wu, J. (2014). Genome editing and animal models. Chinese science bulletin59(1), 1-6.
  • Park, K.-E., Park, C.-H., Powell, A., Martin, J., Donovan, D. M., & Telugu, B. P. (2016). Targeted Gene Knockin in Porcine Somatic Cells Using CRISPR/Cas Ribonucleoproteins. International Journal of Molecular Sciences17(6), 810. http://doi.org/10.3390/ijms17060810.
  • Guenther, C. A., Tasic, B., Luo, L., Bedell, M. A., & Kingsley, D. M. (2014). A molecular basis for classic blond hair color in Europeans. Nature Genetics46(7), 748–752. http://doi.org/10.1038/ng.2991.
  • Villamizar, C. A. (2014). Characterization of the vascular pathology in the acta2 r258c mouse model and cerebrovascular characterization of the acta2 null mouse. UT GSBS Dissertations and These (Open Access)Paper 508 (2014)
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