B6-htau Mouse
Product Name
B6-htau Mouse
Product ID
C001410
Strain Name
C57BL/6JCya-Mapttm1(hMAPT)/Cya
Backgroud
C57BL/6JCya
Note
One of Cyagen's HUGO-GT™ (Humanized Genomic Ortholog for Gene Therapy) Strains
Status
When using this mouse strain in a publication, please cite “B6-htau Mouse (Catalog C001410) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
Gene Alias
TAU, MSTD, PPND, DDPAC, MAPTL, MTBT1, MTBT2, tau-40, FTDP-17, PPP1R103, Tau-PHF6
NCBI ID
Chromosome
Chr 17
MGI ID
Datasheet
Strain Description
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].
This strain is a humanized mouse model in which the endogenous mouse Mapt gene has been replaced with its human counterpart, including the 3’UTR region. This model can be utilized to study various neurodegenerative diseases, such as FTD and AD. This model is commonly named htau. In addition, based on the independently developed TurboKnockout fusion BAC recombination technology, Cyagen can also generate hot mutation models based on this strain and provide customized services for specific mutations to meet the experimental needs in pharmacology and other fields.
Reference
Bang J, Spina S, Miller BL. Frontotemporal dementia. Lancet. 2015 Oct 24;386(10004):1672-82.
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.
Molecular Genetics Department, University of Antwerp. AD Mutations.
Andorfer C, Kress Y, Espinoza M, de Silva R, Tucker KL, Barde YA, Duff K, Davies P. Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms. J Neurochem. 2003 Aug;86(3):582-90.
Easton A, Jensen ML, Wang C, Hagedorn PH, Li Y, Weed M, Meredith JE, Guss V, Jones K, Gill M, Krause C, Brown JM, Hunihan L, Natale J, Fernandes A, Lu Y, Polino J, Bookbinder M, Cadelina G, Benitex Y, Sane R, Morrison J, Drexler D, Mercer SE, Bon C, Pandya NJ, Jagasia R, Ou Yang TH, Distler T, Grüninger F, Meldgaard M, Terrigno M, Macor JE, Albright CF, Loy J, Hoeg AM, Olson RE, Cacace AM. Identification and characterization of a MAPT-targeting locked nucleic acid antisense oligonucleotide therapeutic for tauopathies. Mol Ther Nucleic Acids. 2022 Aug 4;29:625-642.
DeVos SL, Miller RL, Schoch KM, Holmes BB, Kebodeaux CS, Wegener AJ, Chen G, Shen T, Tran H, Nichols B, Zanardi TA, Kordasiewicz HB, Swayze EE, Bennett CF, Diamond MI, Miller TM. Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy. Sci Transl Med. 2017 Jan 25;9(374):eaag0481.
Yoshiyama Y, Higuchi M, Zhang B, Huang SM, Iwata N, Saido TC, Maeda J, Suhara T, Trojanowski JQ, Lee VM. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron. 2007 Feb 1;53(3):337-51.
Arvinas. (2021). Arvinas 2021 Investor Day Presentation.
Alnylam Pharmaceuticals, Inc. (2023). Microtubule associated protein tau (mapt) irna agent compositions and methods of use thereof (Patent No. WO2023049871). World Intellectual Property Organization.
Eli Lilly and Company. (2023). Mapt rna interference agents (Patent No. WO2023114700). World Intellectual Property Organization.
Strain Strategy
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 3'UTR.
Figure 1. Gene editing strategy for B6-htau mice.
Application Area
Research on Frontotemporal dementia (FTD);
Research on Alzheimer's disease (AD);
Research on other neurodegenerative diseases.
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