B6;D2-Tg(Thy1-MAPT*L266V*G272V)13Ema/RoriJ

Stock number: 038799
Product name: 3RTau (Line 13)
Research areas: Neurobiology Research

Description

3RTau (Line 13) transgenic mice carry the mouse Thy1 promoter driving expression of human MAPT containing three ~32 amino acid repeats bearing the L266V and G272V mutations. These mice may be useful in studying neurodegenerative tauopathies, such as familial Pick's disease.

Detailed description

Tau protein, encoded by the microtubule associated protein tau (Mapt) gene, binds to tubulin and supports stabilization of microtubules that are implicated in the development and maintenance of neuronal axons and dendrites. Mapt mutations have been associated with multiple tauopathies, such as Alzheimer's disease, Parkinson's disease and frontotemporal dementias. Multiple Mapt transcripts are produced and differentially expressed in the nervous system, depending on stage of neuronal maturation and neuronal type.

This 3RTau (Line 13) transgenic line expresses human MAPT containing three ~32 amino acid repeats bearing the L266V and G272V mutations driven by the mouse thymus cell antigen 1, theta (Thy1) promoter. Hemizygous 3RTau (Line 13) mice are viable, homozygous mice have not been evaluated by the donating laboratory (October 2023). Hemizygous 3RTau (Line 13) transgenic mice demonstrate accumulation of 3R Tau in the neocortex and hippocampus starting at 6-8 months of age. Hemizygous mice also display hyperactivity, and memory deficits in the water maze by 8-10 months of age. Copy number and integration site of the transgene have not been determined. These 3RTau (Line 13) mice may be useful for studying neurodegenerative tauopathies, such as Pick's disease.

Development

The 3RTau (Line 13) transgene was generated using human microtubule-associated protein tau (MAPT2) cDNA, containing the L266V and G272V mutations, under the control of the mouse thymus cell antigen 1, theta Thy1 gene promoter. The 3R Tau mutant cDNA fragment was ligated into pCRII (Invitrogen, La Jolla, CA), sequenced for accuracy, inserted into the mThy-1 expression cassette between exons 2 and 4, and purified. The purified linearized DNA was microinjected into the pronuclei of fertilized (C57BL/6 x DBA/2)F1 mouse oocytes. Founder line 13 was determined to have the highest expression and further expanded. The donating laboratory has indicated that the integration site and copy number are not known. These transgenic mice were then maintained on a mixed B6;D2 background. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize B6D2F1 (Stock No. 100006) oocytes.

Note on Exon Numbering: The human MAPT cDNA sequence in this transgene has amino acid numbering referred to as MAPT*L266V*G272V, which was based on an older transcript reference (Ensembl transcript MAPT-204), where exon9 aa mutations are denoted as L266V and G272V. However, the current reference would be to canonical transcript MAPT-201 where exon9 aa mutations are denoted as L658V G664V. As such, this transgene could be referred to as MAPT*L658V*G664V with regards to the current understanding of canonical MAPT-201 exon9 sequence.
Also, based on recent sequencing completed by The Jackson Laboratory (March 2025), a 93bp deletion was identified, where the human MAPT cDNA sequence is missing a region from exon 10 (all but first 5nt) through part of exon 11.

Allele

Symbol: Tg(Thy1-MAPT*L266V*G272V)13Ema
Name: transgene insertion 13, Eliezer Masliah
MGI accession ID: MGI:5774860
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Synonyms: 3R Tau
Marker symbol: Tg(Thy1-MAPT*L266V*G272V)13Ema
Marker name: transgene insertion 13, Eliezer Masliah
Chromosome: UN
Strain of origin: (C57BL/6 x DBA/2)F1
Molecular note: The human Tau containing three ~32 amino acid repeats bearing the L266V and G272V mutations associated with familial forms of Picks Disease is under the control of the neuronal mouse Thy1 promoter. Line 13 is a high expressing line and expresses 8 fold higher levels than line 2.