B6.FVB-Tg(Prnp-MAPT*K274Q*K281Q)286Lgn/J

Stock number: 028233
Product name: tauKQ^high
Research areas: Neurobiology Research

Description

These tauKQ^high mice express human MAPT (tau) with mutations to mimic abnormal acetylation in the brain and have applications related to the study of Alzheimer’s disease and other tauopathies.

Detailed description

Hyperacetylation of MAPT (tau) lysines K274 and K281, which are within the microtubule-binding domain region, has been found in the brains of Alzheimer’s disease patients with dementia. These transgenic mice express the human tauKQ MAPT isoform under the direction of the mouse prion protein promoter. The human tauKQ (MAPT) transgene contains lysine-to-glutamine mutations that recapitulate abnormal MAPT K274 and K281 acetylation (ac-K274 and ac-K281). Transgene expression is detected in hippocampal lysates by western blot analysis, and in hippocampus, cortex, and cerebellum by in situ hybridization. Transgenic mice exhibit caspase-cleaved MAPT protein in the hippocampus and increased misfolded MAPT protein in mossy fibers. Hippocampal long-term potentiation, spatial memory and memory retention are impaired in transgenic mice. Mice that are hemizygous for the transgene are viable and fertile. Homozygous viability/fertility has not been tested (November, 2016).

Development

A transgenic construct containing mutant human MAPT (tauKQ) cDNA under the control of the mouse prion protein, Prnp, gene promoter, was injected into fertilized FVB/N mouse eggs. The human MAPT (tauKQ) transgene contains lysine-to-glutamine mutations that recapitulate MAPT K274 and K281 acetylation, and was constructed by introducing A820C and A841C mutations into the recombinant full-length wildtype human 2N4R MAPT (tauWT) cDNA. Founder line 286 tauKQ^high (RRID: MGI_5708388) was subsequently established. The mice were then backcrossed to C57BL/6J for 9 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Tg(Prnp-MAPT*K274Q*K281Q)286Lgn
Name: transgene insertion 286, Li Gan
MGI accession ID: MGI:5708388
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(Prnp-MAPT*K274Q*K281Q)286Lgn
Marker name: transgene insertion 286, Li Gan
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: MAPT,microtubule associated protein tau,human
Molecular note: The transgenic construct contains a mutant human MAPT (tauKQ) transgene with lysine-to-glutamine amino acid substitutions that recapitulate MAPT K274 and K281 acetylation under the control of the mouse prion protein, Prnp, gene promoter. The nucleotide substitutions are, respectively, A to C at position 820 and A to C at position 841. Founder line 286 has higher expression of the transgene than founder line 1. The transgene is expressed in hippocampus, cortex and cerebellum.