B6-hTFRC/htau Mouse
Product Name
B6-hTFRC/htau Mouse
Product ID
I001209
Strain Name
C57BL/6Cya-Tfrctm1(hTFRC)Mapttm1(hMAPT)/Cya
Backgroud
C57BL/6Cya
When using this mouse strain in a publication, please cite “B6-hTFRC/htau Mouse (Catalog I001209) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Alias
TAU, MSTD, PPND, DDPAC, MAPTL, MTBT1, MTBT2, tau-40, FTDP-17, PPP1R103, Tau-PHF6, T9, TR, TFR, p90, CD71, TFR1, TRFR, IMD46
Chromosome
Chr 17, Chr 3
Datasheet
Strain Description
The Transferrin receptor (TFRC) gene encodes Transferrin Receptor 1 (TFR1), a protein that is expressed at low levels in most normal cells but shows increased expression in highly proliferative cells, such as basal epidermal cells, intestinal epithelium, and certain activated immune cells. Brain capillary endothelial cells, which constitute the blood-brain barrier (BBB), also express this receptor at high levels [1]. TFR1 plays a critical role in maintaining iron metabolism and homeostasis by facilitating receptor-mediated endocytosis of iron-bound transferrin (Tf) via Tf cycling, thereby promoting iron uptake [2]. Cellular iron deficiency can lead to apoptosis, while cellular transformation requires substantial iron to sustain proliferation, with iron overload contributing to tumor progression. The high expression of TFR1 in many tumors makes it a potential tumor marker, offering a target for therapies to inhibit tumor growth and metastasis [1]. Moreover, TFR1 is implicated in anemia and iron metabolism disorders. Studies have shown that elevated TFR1 expression in cardiomyocytes is associated with exacerbated inflammation in myocarditis patients [3].
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 [4]. 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 [5].
The B6-hTFRC/htau mice are a model expressing human TFRC protein and tau protein, generated by crossing B6-hTFRC(CDS) mice (Catalog No.: C001584) with B6-htau mice (Catalog No.: C001410). These mice can be used for research on neurodegenerative diseases and iron metabolism disorders, as well as for the development and preclinical evaluation of TFRC/MAPT-targeted therapeutic agents.
Reference
Candelaria PV, Leoh LS, Penichet ML, Daniels-Wells TR. Antibodies Targeting the Transferrin Receptor 1 (TfR1) as Direct Anti-cancer Agents. Front Immunol. 2021 Mar 17;12:607692.
Xu W, Barrientos T, Mao L, Rockman HA, Sauve AA, Andrews NC. Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart. Cell Rep. 2015 Oct 20;13(3):533-545.
Kobak KA, Franczuk P, Schubert J, Dzięgała M, Kasztura M, Tkaczyszyn M, Drozd M, Kosiorek A, Kiczak L, Bania J, Ponikowski P, Jankowska EA. Primary Human Cardiomyocytes and Cardiofibroblasts Treated with Sera from Myocarditis Patients Exhibit an Increased Iron Demand and Complex Changes in the Gene Expression. Cells. 2021 Apr 6;10(4):818.
Strang KH, Golde TE, Giasson BI. MAPT mutations, tauopathy, and mechanisms of neurodegeneration. Lab Invest. 2019 Jul;99(7):912-928.
Lisowiec J, Magner D, Kierzek E, Lenartowicz E, Kierzek R. Structural determinants for alternative splicing regulation of the MAPT pre-mRNA. RNA Biol. 2015;12(3):330-42.
Strain Strategy
TurboKnockout targeting technology was used to replace part of exon 2 of the mouse Tfrc gene with a human TFRC chimeric cDNA WPRE-BGH pA cassette. Gene-editing techniques were employed to knock out exons 10-13 of the mouse Tfrc gene.
The sequences from the ATG start codon to downstream of the endogenous mouse Mapt gene were replaced with the sequences from the ATG start codon to downstream of the human MAPT gene. The humanized regions include the 3'UTR.
Figure 1. Gene editing strategy of B6-hTFRC (CDS) mice.
Figure 2. Gene editing strategy of B6-htau mice.
Application Area
Neurodegenerative diseases such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD);
Research on iron metabolism disorders and tumor development;
Preclinical studies of TFRC/MAPT-targeted therapeutic agents.
Contact Us
Connect with our experts for your custom animal model needs. Please fill out the form below to start a conversation or request a quote.
Cyagen values your privacy. We’d like to keep you informed about our latest offerings and insights. Your preferences:
You may unsubscribe from these communications at any time. See our Privacy Policy for details on opting out and data protection.
By clicking the button below, you consent to allow Cyagen to store and process the personal information submitted in this form to provide you the content requested.