Humanized Mice Technology from GeneTargeting.com

 

Genetically Humanized Mice

  • Change a single base or an entire gene to match the human sequence.

  • No design is too difficult – go beyond size limitations using our proprietary technology.

  • Create a single model for exploratory and translational research.

You already know the value of a good mouse model for studying human disease. Boost the impact of your next project by replacing your gene of interest with the corresponding sequence from the human genome. Design your ideal humanized mice without limitation – from a single base change to replacement of a 200kb gene, including the potential for conditional alleles, cassette knockins, and more. Genetically humanized mice from ingenious will be the cornerstone of your research for years to come.

Full or Partial Gene Humanization – Replace Entire Coding and Noncoding Sequence Using ingenious’ TruHumanization™ Technology.

  • ingenious makes it easy to replace entire mouse genes with human.

  • There is no longer the limitation of leaving out human noncoding regions in your design.

  • Create a mouse model that better captures the human disease condition.

  • Enhance your humanized mice by adding a reporter or making a conditional allele.

Traditional approaches to humanize the mouse manipulate only the coding regions of the genes of interest. Research has demonstrated that non-coding regions of the genome have implications in gene regulation and function. Therefore, it is becoming increasingly important to include non-coding regions of a human gene of interest when targeting the mouse gene ortholog.

Let ingenious create the ultimate model for you by fully humanizing your gene of interest using TruHumanization™ technology. Up to 200kb can be replaced in a single step including coding and noncoding sequence. A humanized gene can also be made into a conditional allele for increased control over expression, and can incorporate known disease-causing mutations. Fully humanized mice lead to more faithful gene regulation and processing as well as the potential to perform functional and regulatory studies on multiple transcripts, providing you with a more flexible mouse model to study for years to come.

Express Human cDNA from Mouse Locus

  • Expression of human coding sequence under the control of the mouse promoter.

  • Can incorporate mutations, co-express reporter gene.

  • Can include loxP design for tissue specific or temporal control.

  • A cDNA knockin may be right for you if you need more than a simple point mutation.

Human cDNA can be knocked into any point of the mouse gene from the first ATG to the final exon. A cDNA at the 5’ end of the gene will be driven by the native promoter and will incorporate a poly-A sequence to block translation of the mouse gene. Add a fluorescent reporter to the knocked in sequence to track expression at the level of individual cells.

Point Mutation – Coding or Noncoding

  • Duplicate a mutation identified in human patients.

  • Change a key amino acid to match human sequence.

  • Conditional point mutations give you control over affected tissues.

ingenious has delivered hundreds of mouse models with point mutations. Contact us to discuss the right model for you, whether it be a point mutation in coding sequence, a promoter or a splice site. Your next model can more closely match the human sequence – wild-type or mutated.

Enhanced Capabilities Available at ingenious

  • Conditional activation of any humanized project by incorporating Cre-loxP technology into the design.

  • Conditional activation of a human cDNA from the mouse Rosa26 locus, allowing more specific control of expression of the relevant human protein in the mouse model.

  • Addition of F.A.S.T.™ cassette to enable inducible/reversible control of human gene.

  • Addition of reporters or tags for co-expression with human protein.

  • And more! No design is too difficult or out of reach when you work with ingenious’ experts.

After You Receive Your Mice

ingenious provides the advanced technology options to address projects of virtually any size, but our services do not end there. Once you receive your humanized mice, you will need to generate a cohort to utilize for experiments. ingenious’ post project support services provides the tools you need for cohort development, as well as cryopreservation services for protecting your investment.

Resources for further reading

Church DM, Goodstadt L, Hillier LW, Zody MC, Goldstein S, She X, Bult CJ, Agarwala R, Cherry JL, DiCuccio M et al. 2009. Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol 7: e1000112.

Devoy A, Bunton-Stasyshyn RK, Tybulewicz VL, Smith AJ, Fisher EM. 2011. Genomically humanized mice: technologies and promises. Nat Rev Genet 13: 14-20.

Macdonald LE, Karow M, Stevens S, Auerbach W, Poueymirou WT, Yasenchak J, Frendewey D, Valenzuela DM, Giallourakis CC, Alt FW et al. 2014. Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes. Proc Natl Acad Sci U S A 111: 5147-5152.

ENCODE (ENCyclopedia Of DNA Elements): The goal of this international database is to map functional elements within the human genome to the biological functions they regulate.