Mapt-flox Mouse

Mapt, short for microtubule-associated protein tau, encodes the tau protein which is crucial for maintaining microtubule function and axonal transport. Tau protein, through its association with microtubules, participates in various cellular processes related to neuronal structure and function [2,5]. The gene's expression and alternative splicing are complex, generating six main isoforms in the central nervous system, which play different roles in both physiological and pathological conditions [3,4].

In a study, through homologous recombination, the entire murine Mapt gene was replaced with the human ortholog, creating knock-in mice. These mice, with humanized Mapt, expressed all six human tau isoforms. When crossed with single amyloid precursor protein (App) knock-in mice, the double-knock-in mice showed higher tau phosphorylation. Also, tau humanization significantly accelerated cell-to-cell propagation of AD brain-derived pathological tau, both in the absence and presence of Aβ-amyloidosis. This demonstrated that Aβ-amyloidosis affects tau pathology and that pathological human tau interacts better with human tau than murine tau, suggesting species-specific differences [1].

In conclusion, Mapt plays a vital role in maintaining normal neuronal function through the tau protein it encodes. The development of Mapt humanized knock-in mouse models has provided valuable insights into the role of Mapt in neurodegenerative diseases, especially in understanding the relationship between tau pathology and Aβ-amyloidosis, which are key pathological features in diseases like Alzheimer's disease.