hutau-P301S Mouse

Frontotemporal Dementia (FTD) is the second most prevalent form of early-onset dementia, following Alzheimer’s disease (AD). This condition is distinguished by the selective degeneration of the frontal and temporal lobes, resulting in personality and behavioral changes, language impairments, and executive dysfunction. Approximately 40%-50% of FTD cases have a familial component, with known causative genes including MAPT, FUS, and TARDBP. Of these, MAPT is the earliest discovered and most frequently implicated in FTD. Mutations in the MAPT gene are detectable in roughly 30% of familial FTD cases ^[1].

The tau protein, a microtubule-associated protein encoded by MAPT, is primarily localized to neuronal axons and plays a critical role in microtubule stability and assembly. By binding to microtubules, the tau protein helps to maintain neuronal cell shape. Mutations in MAPT can promote tau aggregation, leading to pathological tau protein accumulation and death of glutamatergic cortical neurons ^[2]. Additionally, certain MAPT mutations can affect pre-mRNA exon splicing, altering the ratio of 3R to 4R tau protein isoforms and increasing the relative production of 4R-tau protein, which is more prone to fibril formation ^[3]. Common mutations include P301L, P301S, and Intron10+3 G>A ^[4]. Research indicates that the P301S mutation significantly reduces the ability of recombinant tau protein to promote microtubule assembly. Patients with this mutation exhibit clinical heterogeneity ^[10-12]. Similar to the P301L mutation, the P301S mutation also leads to pathological aggregation of the tau protein, resulting in neurodegenerative diseases.

Therapies targeting the MAPT gene primarily consist of small-molecule drugs and monoclonal antibodies, with indications including AD and FTD. Transgenic mice are frequently used in drug development, and the utilization of humanized animal models helps advance potential MAPT-related therapies toward clinical trials ^[5-9]. This strain is a mouse Mapt gene humanized model carrying the P301S mutation and can be used for research on FTD and AD. The homozygous hutau-P301S mice are viable and fertile. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also generate other hot mutation models (e.g., B6-htau*P301L mice, Catalog Number: C001835) and provide customized services for specific mutations.