• CRISPR-Cas9 Rat Models
    • AAALAC and worldwide shipping
    CRISPR-Cas9 Rat Models

Rat Models

Genetically engineered rat models are gaining popularity as the preferred biological model for several research areas. ASC can genetically engineer rat models with a physiologically relevant modifications using an expanded technology portfolio with complementary CRISPR/Cas9 and TARGATT™ technologies, as well as, traditional homologous recombination and random transgenic technologies.

  • ISO:9001 quality service
  • F1 breeding for germline transmission
  • New! surgically/ chemically induced rat models of neurological diseases
  • Customized projects for in vivo assessments (automated behavior/ locomotor activity, EEG/ ECG, and pharmacokinetics) as well as in vitro evaluations (electrophysiology, immunohistochemistry & other biochemical assays)
Rat Models Categories

Conditional Knockout
Rat Models

Conditional knock-out/ expression mouse model generation to accurately model temporal and spatially controlled gene expression in rats.

Conditional Knockout
Rat Models

Site-Specific TARGATT™
Knock-in Rat Models

Fast and Reliable! Site-specific, safe harbor locus large transgene knock-in for gene overexpression and custom Cre rat line generation.

Site-Specific TARGATT™
Knock-in Rat Models

Knockout, Knock-in, Point
Mutation Rat Models

Full service CRISPR rat model generation with precise gene knockout, knock-in, and point mutation modifications for basic and preclinical research.

Knockout, Knock-in, Point
Mutation Rat Models

Site-Specific TARGATT™
Knock-in Cre-Rat Models

Leverage our neurological or cardiovascular tissue-specific Cre-expressing promoter constructs with your rat to accelerate your research.

Site-Specific TARGATT™
Knock-in Cre-Rat Models

 

Products and Services
Technical Details

Some examples of available genetic modifications in rats include but not limited to:

  • Constitutive and conditional knockouts
  • Small fragment insertions, point mutations
  • Large fragment knock-in: locus specific or safe harbor locus
  • Gene tagging/ reporter gene insertion
  • Gene replacement
  • Gene fusion/ translocation
  • Gene overexpression, inducible expression, promoter modifications
  • Gene editing/ correction to model human diseases

Applications: Functional genomics, disease modeling, target identification and validation for drug discovery and screening, and many more.

Choosing the right genome editing technology:

Applied StemCell uses two complementary genome editing technologies to generate advanced cell line and animal models very efficiently and effectively: the CRISPR/Cas9 technology and our propriety site-specific gene integration technology, TARGATT™ for large fragment (up to 22 kb) knock-in into a safe harbor locus.

Project Purpose

CRISPR/Cas9

TARGATT™

Knock-Out (KO)

Yes

 

Point Mutation

Yes

 

Conditional KO

Yes

 

Knock-In

(<200 Nucleotide ssODN Donor)

Yes

 

Knock-In Transgenes in

Safe Harbor Loci (>2kb)

Challenging

(but limitations on size)

Yes

 (up to 22kb)

Knock-In

 (Plasmid DNA)

Challenging

(but limitations on size)

Yes

 (2 steps: KI docking site; KI transgene) 

We also offer mouse model generation service using an expanded technology portfolio such as traditional homologous recombination via ESCs, bacterial artificial chromosome and random transgenic technologies. With our expertise in mouse model generation service and various genome editing technologies, we can assure you a custom genetically engineered mouse model perfect for your research needs.

Bacterial Artificial Chromosome (BAC) Knock-in and Conditional Knock-In Rat Models.

We also offer BAC knock-in and conditional knock-in rat model generation service for very large gene insertions (up to 300 kb), making them ideal for introduction of entire genes including the regulatory regions into the rat genome. Alternatively, you can choose to have us do the BAC modification strategy and cloning, and you can do the pronuclear injections and transgenic rat screening yourself.

Our services include:

  • BAC design and cloning strategy
  • Cloning and sequence validation of the BAC tailor-made to your specifications
  • Pronuclear microinjection of BAC into rat embryos
  • Genotyping
Publications

CRISPR Mouse/ Rat Models:  Knock-in, Knockout, and Conditional Knockout 

CRISPR Technology

CRISPR Knock-in H11 Locus in Pigs

  • Ruan, J., Li, H., Xu, K., Wu, T., Wei, J., Zhou, R., ... & Chen-Tsai, R. Y. (2015). Highly efficient CRISPR/Cas9-mediated transgene knockin at the H11 locus in pigs. Scientific reports5, 14253.

 Knock-in, Knockout, Conditional Knock-out

  • Park, J., Jung, E., Lee, S. H., & Chung, W. S. (2020). CDC50A dependent phosphatidylserine exposure induces inhibitory post-synapse elimination by microglia. bioRxiv.
  • Ramachandra Rao, S., Fliesler, S. J., Kotla, P., Nguyen, M. N., & Pittler, S. J. (2020). Lack of Overt Retinal Degeneration in a K42E Dhdds Knock-In Mouse Model of RP59. Cells9(4), 896.
  • Beurg, M., Barlow, A., Furness, D. N., & Fettiplace, R. (2019). A Tmc1 mutation reduces calcium permeability and expression of mechanoelectrical transduction channels in cochlear hair cells. Proceedings of the National Academy of Sciences116(41), 20743-20749.
  • Goldring, A. C., Beurg, M., & Fettiplace, R. (2019). The contribution of TMC1 to adaptation of mechanoelectrical transduction channels in cochlear outer hair cells. The Journal of physiology.
  • Hwang, S., He, Y., Xiang, X., Seo, W., Kim, S. J., Ma, J., ... & Kunos, G. (2019). Interleukin‐22 ameliorates neutrophil‐driven nonalcoholic steatohepatitis through multiple targets. Hepatology https://doi.org/10.1002/hep.31031.
  • Dumesic, P. A., Egan, D. F., Gut, P., Tran, M. T., Parisi, A., Chatterjee, N., ... & Dou, F. (2019). An Evolutionarily Conserved uORF Regulates PGC1α and Oxidative Metabolism in Mice, Flies, and Bluefin Tuna. Cell metabolism.
  • Liang, T., Zhang, H., Xu, Q., Wang, S., Qin, C., & Lu, Y. (2019). Mutant Dentin Sialophosphoprotein Causes Dentinogenesis Imperfecta. Journal of dental research, 0022034519854029.
  • Qian, W., Miner, C. A., Ingle, H., Platt, D. J., Baldridge, M. T., & Miner, J. J. (2019). A human STAT1 gain-of-function mutation impairs CD8+ T cell responses against gammaherpesvirus-68. Journal of virology, JVI-00307.
  • Kweon, S. M., Chen, Y., Moon, E., Kvederaviciutė, K., Klimasauskas, S., & Feldman, D. E. (2019). An Adversarial DNA N6-Methyladenine-Sensor Network Preserves Polycomb Silencing. Molecular Cell. https://doi.org/10.1016/j.molcel.2019.03.018
  • Deng, F., He, S., Cui, S., Shi, Y., Tan, Y., Li, Z., ... & Peng, L. (2018). A Molecular Targeted Immunotherapeutic Strategy for Ulcerative Colitis via Dual-Targeting Nanoparticles Delivering miR-146b to Intestinal Macrophages. Journal of Crohn's and Colitis.
  • Jo, S., Fonseca, T. L., Bocco, B. M. D. C., Fernandes, G. W., McAninch, E. A., Bolin, A. P., ... & Németh, D. (2018). Type 2 deiodinase polymorphism causes ER stress and hypothyroidism in the brain. The Journal of Clinical Investigation.
  • Langston, R. G., Rudenko, I. N., Kumaran, R., Hauser, D. N., Kaganovich, A., Ponce, L. B., ... & Beilina, A. (2018). Differences in Stability, Activity and Mutation Effects Between Human and Mouse Leucine-Rich Repeat Kinase 2. Neurochemical research, 1-14.
  • Amara, N., Tholen, M., & Bogyo, M. (2018). Chemical tools for selective activity profiling of endogenously expressed MMP-14 in multicellular models. ACS Chemical Biology. doi: 10.1021/acschembio.8b00562.
  • Allocca, S., Ciano, M., Ciardulli, M. C., D’Ambrosio, C., Scaloni, A., Sarnataro, D., ... & Bonatti, S. (2018). An αB-Crystallin Peptide Rescues Compartmentalization and Trafficking Response to Cu Overload of ATP7B-H1069Q, the Most Frequent Cause of Wilson Disease in the Caucasian Population. International journal of molecular sciences19(7).
  • Peng, L., Zhang, H., Hao, Y., Xu, F., Yang, J., Zhang, R., ... & Chen, C. (2016). Reprogramming macrophage orientation by microRNA 146b targeting transcription factor IRF5. EBioMedicine, 14, 83-96.
  • Hu, J. K., Crampton, J. C., Locci, M., & Crotty, S. (2016). CRISPR-mediated Slamf1Δ/Δ Slamf5Δ/Δ Slamf6Δ/Δ triple gene disruption reveals NKT cell defects but not T follicular helper cell defects. PloS one, 11(5), e0156074.
  • Besschetnova, T. Y., Ichimura, T., Katebi, N., Croix, B. S., Bonventre, J. V., & Olsen, B. R. (2015). Regulatory mechanisms of anthrax toxin receptor 1-dependent vascular and connective tissue homeostasis. Matrix Biology42, 56-73.
  • McKenzie, C. W., Craige, B., Kroeger, T. V., Finn, R., Wyatt, T. A., Sisson, J. H., ... & Lee, L. (2015). CFAP54 is required for proper ciliary motility and assembly of the central pair apparatus in mice. Molecular biology of the cell26(18), 3140-3149.
  • Bishop, K. A., Harrington, A., Kouranova, E., Weinstein, E. J., Rosen, C. J., Cui, X., & Liaw, L. (2016). CRISPR/Cas9-mediated insertion of loxP sites in the mouse Dock7 gene provides an effective alternative to use of targeted embryonic stem cells. G3: Genes, Genomes, Genetics6(7), 2051-2061.

TARGATT™ Site Specific Knock-in Mouse 

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)

Mouse/ Rat Models: Homologous Recombination Conditional Knockout Mouse 

  • Geraets, R. D. (2019). Neuronal Ceroid Lipfuscinosis: A Tailored Animal Model of CLN2 Disease and Evaluation of Select Personalized Therapies (Doctoral dissertation, ProQuest Dissertations Publishing).
  • Zhao, M., Tao, F., Venkatraman, A., Li, Z., Smith, S. E., Unruh, J., ... & Marshall, H. (2019). N-Cadherin-Expressing Bone and Marrow Stromal Progenitor Cells Maintain Reserve Hematopoietic Stem Cells. Cell reports, 26(3), 652-669.

  • Li, C., Zheng, Z., Ha, P., Chen, X., Jiang, W., Sun, S., ... & Chen, E. C. (2018). Neurexin Superfamily Cell Membrane Receptor ContactinAssociated Protein Like4 (Cntnap4) is Involved in Neural EGFL Like 1 (Nell1)responsive Osteogenesis. Journal of Bone and Mineral Research https://doi.org/10.1002/jbmr.3524.

  • Geraets, R. D., Langin, L. M., Cain, J. T., Parker, C. M., Beraldi, R., Kovacs, A. D., ... & Pearce, D. A. (2017). A tailored mouse model of CLN2 disease: A nonsense mutant for testing personalized therapies. PloS one, 12(5), e0176526.

  • Miller, J. N., Kovács, A. D., & Pearce, D. A. (2015). The novel Cln1R151Xmouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy. Human Molecular Genetics, 24(1), 185–196. http://doi.org/10.1093/hmg/ddu428.

Have Questions?

An Applied StemCell technical expert is happy to help, contact us today!

Google