Research Models


Synonyms: human tau

Species: Mouse
Modification: MAPT: Knock-Out; MAPT: Transgenic
Disease Relevance: Alzheimer's Disease, Frontotemporal Dementia
Strain Name: B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J
Genetic Background: The targeted allele was created in 129S4/SvJae-derived J1 embryonic stem cells which were subsequently injected into C57BL/6 blastocysts. The transgenic allele was generated in embryos derived from a cross between Swiss Webster and B6D2F1. Mice containing both alleles were backcrossed to C57BL/6 mice .
Availability: Jackson Labs: Stock# 005491; Live


This mouse was designed to express only human tau isoforms (Andorfer et al., 2003). It was made by mating two existing lines of tau mice, 8c (Duff et al., 2000) and tau knock-out mice (Tucker et al., 2001). 8c mice express a tau transgene via a PAC cloning vector driven by the tau promoter and produce all human tau isoforms, including 3R and 4R isoforms. Tau knock-out mice were generated by targeted disruption, in which cDNA for enhanced green fluorescent protein (EGFP) was inserted into exon one of MAPT. Htau mice express six isoforms of human tau, but do not express mouse tau. Unlike the double mutant, neither 8c mice nor tau knock-out mice develop tau pathology in the CNS.


These mice develop age-associated tau pathology, including redistribution of tau to cell bodies and dendrites, phosphorylated tau, accumulation of aggregated paired helical filaments, and ultimately, thioflavin-S-positive neurofibrillary tangles at 9-15 months. Tau pathology is most severe in the neocortex and hippocampus, and minimal in the brain stem and spinal cord. Some regional neuronal loss was also observed (Andorfer et al., 2003; Andorfer et al., 2005).


Mice had normal object recognition memory and spatial learning/memory as assessed by the Morris Water Maze at four months, but were impaired at twelve months (Polydoro et al., 2009). Abnormal spatial learning was noted in six month-old mice compared to control mice (Phillips et al., 2011).

Other Phenotypes

General health, weight, basic reflexes, sensory responses, locomotor function, anxiety level and gross motor function were not different from age-matched controls (Polydoro et al., 2009).

Modification Details

Double mutant mice were generated by mating mice that express human tau (8c mice)(Duff et al., 2000), with tau knockout mice that have a targeted disruption of exon 1 of tau (Tucker et al., 2001). Then backcrossed to obtain mice that are homozygous for disrupted murine MAPT while carrying the human tau transgene.

Phenotype Characterization

When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.




  • Gliosis
  • Synaptic Loss


Aggregated tau and paired helical filaments detectable at 9 months by immunoelectron microscopy, although paired helical filaments of aggregated insoluble tau can be isolated from brain tissue as early as two months. Tau first redistributes from axons to cell bodies. Hyperphosphorylated tau begins to accumulate by 6 months, and increases further by 13 and 15 months (Andorfer et al., 2003).

Neuronal Loss

Decrease in cortical thickness and reduced cell number between 10 and 14 months of age. Increased ventricle size increased from age 8 months to 18 months. Decrease in the thickness of the corpus callosum (Andorfer et al., 2005).



Synaptic Loss


Changes in LTP/LTD

In hippocampal slices, LTP induced by high frequency stimulation (HFS) was normal at 4 months but abolished by 12 months. LTP induced by theta burst stimulation (TBS) was normal at both ages. Paired-pulse ratio (PPR) was unaffected at 4 months, but increased at 12 months compared to controls, suggesting a decrease in probability of transmitter release (Polydoro et al., 2009).

Cognitive Impairment

Abnormal spatial learning in 6 month-old mice compared to control mice (Phillips et al., 2011). Normal object recognition and spatial learning and memory by MWM at 4 months, but deficits by 12 months (Polydoro et al., 2009).



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Paper Citations

  1. . Hyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms. J Neurochem. 2003 Aug;86(3):582-90. PubMed.
  2. . Characterization of pathology in transgenic mice over-expressing human genomic and cDNA tau transgenes. Neurobiol Dis. 2000 Apr;7(2):87-98. PubMed.
  3. . Neurotrophins are required for nerve growth during development. Nat Neurosci. 2001 Jan;4(1):29-37. PubMed.
  4. . Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms. J Neurosci. 2005 Jun 1;25(22):5446-54. PubMed.
  5. . Age-dependent impairment of cognitive and synaptic function in the htau mouse model of tau pathology. J Neurosci. 2009 Aug 26;29(34):10741-9. PubMed.
  6. . Olfactory and visuospatial learning and memory performance in two strains of Alzheimer's disease model mice--a longitudinal study. PLoS One. 2011;6(5):e19567. PubMed.

External Citations

  1. Jackson Labs: Stock# 005491

Further Reading


  1. . Olfactory and visuospatial learning and memory performance in two strains of Alzheimer's disease model mice--a longitudinal study. PLoS One. 2011;6(5):e19567. PubMed.