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Humanized Mouse Models

humanized mouse is an animal model that expresses a human genetic sequence or serves as a host for living human cells or tissues. At ingenious we create custom genetically humanized mouse models to support the research goals of scientists around the world.

Humanize your gene without limitations.

Humanized mice are an excellent 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. A genetically humanized mouse model from ingenious will be the cornerstone of your research for years to come.

Why create a humanized mouse model?

Strategies for creating humanized mouse models

The term “genetic humanization” covers a broad array of strategies for introducing and expressing human genetic sequences in an animal model. The genetic change may be as small as one altered nucleotide (to humanize a crucial site in a protein) or as large as hundreds of kilobases (potentially an entire gene or gene cluster including promoter regions). Read on to learn more about different options for creating your next model.

Genetic Humanization by Random Transgenic Insertion

Targeted Genomic Humanization

Genomic Replacement by TruHumanization™ from ingenious

Humanization Strategies Available at ingenious

Coding Sequence KnockinPoint MutationGene Replacement
⦿ Expression of human coding sequence under the control of the mouse promoter⦿ Change a key amino acid to match human sequence⦿ Replace up to 200kb of genomic sequence in a single step
⦿ Can incorporate mutations, co-express reporter gene⦿ Duplicate a mutation identified in human patients⦿ Humanize a single exon or an entire gene including noncoding regions
⦿ Can include loxP design for tissue specific or temporal control⦿ Conditional point mutations give you enhanced control⦿ The ultimate in genetic humanization
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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.

How are genetically humanized mice created?

Currently the majority of new genetically humanized models are point mutants where a critical nucleotide in the mouse sequence is changed to match the human sequence. These point mutations can often be introduced using the CRISPR/Cas9 method, a popular way to make targeted genetic modifications. In some cases a gene can’t be targeted using CRISPR/Cas9 however. The most common reason to avoid using CRISPR/Cas9 is when a homozygous knockout of the gene produces a strong phenotype. In such cases the point mutation would be introduced by the more established method of homologous recombination using embryonic stem cells. ES cell approaches are also used when making a cDNA knockin or a TruHumanization™ genomic replacement. To make a knockin using ES cells it’s necessary to first create a genetic construct called a targeting vector. The targeting vector has the knockin sequence in the middle with targeting sequences on either side, and is introduced into ES cells. The targeting sequences are recognized by enzymes in the cell and essentially trick the cell’s DNA repair machinery into making the knockin sequence a part of the genome. This method can make precise and targeted genetic modifications because the targeting sequences are specific to a single location in the mouse’s genome. The modification could be as small as changing a single nucleotide or as large as replacing 100kb of mouse genomic sequence with human sequence.

Humanized Mice as Human Disease Models


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