ADVANCING NEUROLOGICAL RESEARCH: MOUSE MODELS WITH HUMANIZED GENES AS TOOLS FOR UNDERSTANDING PATHOPHYSIOLOGY AND DEVELOPING THERAPEUTICS

Mouse models with humanized genes have emerged as a crucial tool in life sciences, particularly in drug efficacy studies for human diseases. These mouse models offer comprehensive insights into human-specific biological processes and disease mechanisms, bridging the gap between preclinical studies and clinical relevance. They enable investigations into the complexities underlying human pathophysiology within a controlled experimental environment, and valuable for studying intricate neuropathological processes driven by genetic, cellular, and synaptic interactions. Cyagen has developed an extensive series of HUGO (HUmanized Gene Ortholog) mouse models, which encompass a wide range of neurological disorder. For instance, the HUGO models that feature the complete replacement of the mMapt with the hMAPT genes either with or without disease-associated mutations such as P301L and P301S exhibit cognitive impairment beginning at 3-6 months of age. This reflects the characteristics observed in human patients with Alzheimer’s disease or frontotemporal lobar degeneration. Additionally, the P301S model demonstrates an accelerated progression compared to the P301L model, closely paralleling human conditions and thereby enhancing the translational relevance of these models.
Furthermore, Cyagen has created HUGO models associated with rare diseases, such the hMECP2 gene and the hMECP2 T158M mutation related to Rett syndrome. The hMECP2 T158M HUGO mice demonstrate motor deficits from 1.5 months of age. This indicate a strong correlation between the mouse model and the corresponding human disease. In summary, Cyagen has developed a comprehensive collection of HUGO mouse models that is highly valuable for studies focusing on the pathophysiology and therapeutic strategies of these conditions.