• Mouse Models

Mouse Models

ASC is a leading provider of genetically engineered mouse models for biomedical research and drug discovery. Our custom mouse model generation service includes:

  • F1 breeding for germline transmission
  • Mouse models engineered in an AAALAC-accredited animal facility in the USA
  • Two complementary gene editing technologies, CRISPR and TARGATT™ for precise and advanced physiologically relevant mouse models
  • New! surgically/ chemically induced mouse models of neurological diseases
  • Customized downstream projects for in vivo assessments (automated behavior/ locomotor activity, EEG/ ECG, and pharmacokinetics) as well as in vitro evaluations (electrophysiology, immunohistochemistry, RT-PCR, western blots and more)
  • Dedicated project management and timely reports
Mouse Models Categories

Conditional Knockout
Mouse Models

Conditional knockout/ expression mouse model generation for a variety of temporal and spatially controlled gene expression in mice.

Conditional Knockout
Mouse Models

Site-Specific TARGATT™
Knock-in Mouse Models

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

Site-Specific TARGATT™
Knock-in Mouse Models

Knockout, Knock-in, Point
Mutation Mouse Models

Custom mouse model generation with biorelevant gene knockout, knock-in, and point mutation modifications for basic and preclinical research.

Knockout, Knock-in, Point
Mutation Mouse Models

Products and Services

15 Items

per page
Publications

CRISPR Mouse/ Rat Models:  Knock-in, Knockout, and Conditional Knockout (*cited/published articles)

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 reports, 5, 14253.

Knock-in, Knockout, Conditional Knock-out

  • 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 sciences, 19(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 Biology, 42, 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 cell, 26(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, Genetics, 6(7), 2051-2061.

TARGATT™ Site Specific Knock-in Mouse 

Description of the technology

Commentary, comparison with other transgenic methods

Tet inducible mice generated by TARGATT™

  • Fan, X., Petitt, M., Gamboa, M., Huang, M., Dhal, S., Druzin, M. L., ... & Nayak, N. R. (2012). Transient, inducible, placenta-specific gene expression in mice. Endocrinology153(11), 5637-5644.

Advantage of Hipp11 (H11) locus

  • Hippenmeyer, S., Youn, Y. H., Moon, H. M., Miyamichi, K., Zong, H., Wynshaw-Boris, A., & Luo, L. (2010). Genetic mosaic dissection of Lis1 and Ndel1 in neuronal migration. Neuron68(4), 695-709.

Application for mice generated by TARGATT™

  • 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., Butt, N. A., Phadatare, P. R., Dholakia, K., Vedula, J., ... & Levenson, A. S. (2018). A novel MTA1 knock-in mouse model for the mechanistic and therapeutic studies of MTA1-driven prostate cancer. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Research, 78(13):Abstract nr 5107.

  • 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(1), 4113.

  • 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. Elife6.

  • 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 and Medicine99, 533-543.

  • 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.

  • 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.

  • Fogg, P. C., Colloms, S., Rosser, S., Stark, M., & Smith, M. C. (2014). New applications for phage integrases. Journal of molecular biology426(15), 2703-2716.

  • 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.

  • 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.

  • 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 Theses.

Mouse/ Rat Models: Homologous Recombination Conditional Knockout Mouse (*cited/published articles)

  • 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.

Technical Details

Some examples of available genetic modifications in mice 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, humanized models
  • 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 20 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 20kb)

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.

Have Questions?

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