Humanized Mouse Models

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A humanized mouse defines a Knockin model in which a mouse gene is replaced by either a human gene, genomic sequence or regulatory element.

This substitution can target parts of the gene, and subsequently specific domains of the protein, as well as certain mouse regulatory elements such as the promoter.

The human protein/domain is then expressed in cells and tissues where the mouse protein was expressed.

Infographic: Humanized Knockin mouse model

Typical applications for humanized Knockin mouse models

For academic research:

Phenocopy a human disease to decipher causes and molecular mechanisms
Create a mouse model that is tolerant of human antigen to study human peptide functions

For bio-pharmaceutical research & development:

Phenocopy human diseases for drug development and safety studies
Provides a model to study efficacy when endogenous mouse target shows low affinity to xenobiotics or biologics
Create a mouse model tolerant of human antigen for antibody or antibody drug conjugate (ADC) testing
Human cytokine expression to improve human immune system engraftment

Strengths and limitations of humanized Knockin mouse models

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Physiological expression patterns due to the murine promoter and regulatory elements

Murine gene is inactivated; no hybrid sequences (like, e.g., in transgenic animals)

Combination with access to Knockout model for specificity studies

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Risk of differential expression in mouse vs. human, due to differences in protein regulation

Low conservation between human/mouse protein => risk of hypomorphism up to protein Knockout
→ Limitation can be bypassed by using chimeric molecules to improve functionality in mouse cells

Follow these links if you are looking for another Knockin mouse model or customized mouse model.