Disease Model: Overexpression of Causual Genes

Tissue- and/or Time-Specific Expression of Disease Causal Genes

Some disease models require the over-expression of disease causal genes in specific cell populations (inflammation, neurodegenerative diseases) and / or within well-defined time window. These mouse models enable scientists to study the onset of the pathology and to evaluate compound efficacy.

To this purpose mouse models could be generated using the Humanization & Knockin Technology using either permissive loci ("safe harbour") or target gene loci.

 

Case study: Inducible disease causal gene overexpression results in leukemia and mouse death.

Adapted from Carofino et al. Dis Model Mech 2013. A mouse model for inducible overexpression of Prdm14 results in rapid-onset and highly penetrant T-cell acute lymphoblastic leukemia (T-ALL).

Mouse model mimicking human disease

Model Mimics Human Disease

Mice overexpressing the Prdm14 gene mimic efficiently the human disease (acute lymphoblastic leukemia) reproducing the human phenotype.

After induction, mice had enlarged thymi and spleens (arrows) as well as kidneys, livers and lymph nodes (data not shown).

 

Mimicked lymphoblastic leukemia in mice

 

After induction, mice developed and succumbed to acute lymphoblastic leukemia very rapidly.