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 ^[3-4]. 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 the drug development process, and the utilization of humanized animal models can facilitate the translation of promising treatments into clinical trials ^[5-9]. The tumor necrosis factor-alpha (TNF/TNF-α) gene encodes a pro-inflammatory cytokine belonging to the TNF superfamily. It is primarily produced by macrophages/monocytes during acute inflammation. TNF-α regulates immune cell function by binding to its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR, participating in normal inflammatory and immune responses. TNF-α is involved in various biological processes, including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This factor is associated with several diseases, such as autoimmune conditions, insulin resistance, psoriasis, rheumatoid arthritis, ankylosing spondylitis, tuberculosis, autosomal dominant polycystic kidney disease, and cancer. Mutations in the TNF-α gene impact susceptibility to cerebral malaria, septic shock, and Alzheimer’s disease ^[10-11]. In mice, defects in this gene are associated with impaired responses to bacterial infections, defects in the organization of follicular dendritic cell networks and germinal centers, and a lack of primary B cell follicles. The B6;D1-htau/hTNF mouse is a dual-gene humanized model generated by crossing B6-htau mice (Catalog No.: C001410) with DBA/1-hTNF mice (Catalog No.: C001587). This model can be used for the study of neurodegenerative diseases such as frontotemporal lobar dementia (FTD) and Alzheimer's disease (AD) and autoimmune diseases such as rheumatoid arthritis (RA), as well as for the research and development, screening, and pre-clinical evaluation of Tau/TNF-targeted drugs.

The huTFRC/huTNF(B6;D1) mice are a dual-gene humanized model obtained by mating huTFRC mice (Catalog No.: C001860) with huTNF(DBA/1) mice (Catalog No.: C001587). This model can be used for the research of neurodegenerative diseases, immune-related diseases such as rheumatoid arthritis (RA), and the occurrence and development of tumors, as well as preclinical studies of TFRC/TNF-targeted drugs.

The huPD-1/huTNF(B6;D1) mice are a dual-gene humanized model obtained by mating huPD-1 mice (Catalog number: C001524) with huTNF(DBA/1) mice (Catalog number: C001587). This model is suitable for research on drug screening, efficacy and safety evaluation, immunotherapy, and immune system mechanisms related to PD-1 and TNF.