Humanized Mice

Humanized Mouse Models

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Humanized Mice

Humanized mice are the perfect model system for studying human disease and for developing better therapeutics. Design your ideal model without limitations – from a single base change to replacement of a 200kb gene, including the potential for conditional alleles, cassette knockins, and more. Genetically humanized mouse models from ingenious will be the cornerstone of your research for years to come.

Humanization Strategies Available at ingenious

Coding Sequence Knockin

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Point Mutation

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Gene Replacement

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→ 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.



Why create humanized mice?

Humanized mice are now a crucial tool for biomedical research.

Mice are an excellent model organism for understanding human biology due to their ease of use, their sharing of genomic and physiological properties with humans, and their ability to be readily manipulated genetically. However there are significant and sometimes crucial differences between mice and humans. Humanized mice can bridge these gaps – replacing a mouse gene with human sequence creates a more faithful model to understand how that gene functions in the human body.

Several design strategies are available for creating these models depending on the extent of humanization needed:


CODING SEQUENCE KNOCKIN

  • 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

POINT MUTATION

  • Change a key amino acid to match human sequence
  • Duplicate a mutation identified in human patients
  • Conditional point mutations give you enhanced control

GENE REPLACEMENT

  • Replace up to 200kb of genomic sequence in a single step
  • Humanize a single exon or an entire gene including noncoding regions
  • The ultimate in genetic humanization

HUMANIZED MICE AS HUMAN DISEASE MODELS

The mouse has a long history as a model organism for the study of human disease and basic biology, based on the similar genetics and physiologies of the two organisms. In some cases a key difference between mice and humans can interfere with a particular experiment, for example a slight change in a protein domain or active site may interfere with antibody or small molecule binding. Differences at the tissue level can also be significant, preventing studies of systems such as the human immune system. Humanized mice are one option for overcoming these challenges – mice altered at the genetic or cellular level to more closely match human biology.

Genetic humanization strategies range from mutating a few key bases for a critical protein domain to replacing entire genes including noncoding regions. Gene replacement models are an exciting system enabling the study of splicing and other regulatory mechanisms in the context of a living animal. Genetically humanized mice are straightforward to use in experiments as they carry the modification in their genome and pass it on to their offspring. A mouse that expresses a disease-causing mutant form of a human gene can be the cornerstone of an extensive research program.

For more details contact ingenious today to discuss your next humanized mouse model.


Resources

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.



ingenious targeting laboratory guarantee

For nearly 2 decades, ingenious has been helping investigators worldwide by developing mouse models customized specifically to their needs.



You will receive a quote within 24 hours, and one of our technical consultants will contact you to discuss your next mouse model.

“We are 100% satisfied with iTL’s service in generating this mouse model for us. The model was completed quickly, with the utmost efficiency and each member of their team was extremely responsive and helpful. The full service guarantee, as well as the company’s excellent reputation were major decision factors for us.”

-Joseph A. Fraietta, PhD