Research Models


Synonyms: rTg4510, Tg(tetO-TauP301L)4510, Tau P301L


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Species: Mouse
Genes: MAPT
Mutations: MAPT P301L
Modification: MAPT: Transgenic
Disease Relevance: Alzheimer's Disease, Frontotemporal Dementia
Strain Name: FVB-Tg(tetO-MAPT*P301L)#Kha/JlwsJ, STOCK Tg(Camk2a-tTA)1Mmay Tg(tetO-MAPT*P301L)#Kha/J
Genetic Background: FVB/N
Availability: The Jackson Lab: Stock# 015815 (single transgenic line); Live;  The Jackson Lab: Stock# 024854 (double transgenic line); Under Development


The rTg4510 mouse is a versatile tauopathy model providing researchers with temporal control over mutant tau transgene expression. The mice express a repressible form of human tau containing the P301L mutation that has been linked with familial frontotemporal dementia. The transgene is downstream of a tetracycline operon–responsive element (TRE), and expression is driven by a second transgene containing a tetracycline-controlled transactivator (tTA) under control of a promoter such as CaMKII-α. Tau is constitutively expressed until inactivated by the tetracycline analog doxycycline (dox), which turns off expression. The data described here refer to bitransgenic progeny expressing regulatable tau largely restricted to the forebrain due to the use of the CaMKII-α promoter. These bitransgenic mice express approximately 13 units of transgene (one unit is equivalent to the level of endogenous murine tau) and develop progressive age-related neurofibrillary tangles, neuronal loss, and behavioral impairments. Notably, after the transgene was switched off with dox, neuronal death ceased and the ability to acquire and retain new spatial memories was restored (SantaCruz et al., 2005).

Modification Details

The transgene encodes human MAPT with four microtubule binding domains and lacking amino terminal inserts (4R/0N) with the P301L mutation. Expression is driven by a tetracycline operator upstream of a cytomegalovirus minimal promoter and contains exons 2-3 of the mouse prion protein gene (Prnp) untranslated sequence.


Early burden of frontal taul pathology in the form of argyrophilic tangle-like inclusions in cortex by four months and in the hippocampus by 5.5 months. Also neuronal loss, including about a 60 percent decrease in CA1 neurons by about 5.5 months. Gross forebrain atrophy is observed by ten months. The number of CA1 neurons stabilized after a brief (six to eight weeks) suppression of transgenic tau.


No significant abnormalities at 1.3 months in the Morris Water Maze. Spatial memory impairments by 2.5 to four months. No significant motor impairment up to six months. When the transgene was suppressed with dox at 2.5 months spatial memory improved.


Homozygous mice are not viable.

Phenotype Timeline

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



  • Plaques





Pretangles as early as 2.5 months. Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months (SantaCruz et al., 2005).

Neuronal Loss

Decreased (~60%) CA1 hippocampal neurons by 5.5 months with significant loss in brain weight. Progressive loss of neurons and brain weight in 7 and 8.5 month mice with ~23% of CA1 pyramidal cells remaining at 8.5 months. Gross atrophy of the forebrain by 10 months (SantaCruz et al., 2005).

Synaptic Loss

Significant loss of dendritic spines at 8-9 months (~30% decrease in spine density in somatosensory cortex)(Kopeikina et al., 2013).

Cognitive Impairment

No significant abnormalities at 1.3 months but the retention of spatial memory examined by Morris Water Maze became impaired from 2.5 to 4 months. No significant motor impairments up to 6 months. Spatial memory improved when transgene suppressed by dox (SantaCruz et al., 2005).



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Paper Citations

  1. . Tau suppression in a neurodegenerative mouse model improves memory function. Science. 2005 Jul 15;309(5733):476-81. PubMed.

External Citations

  1. The Jackson Lab: Stock# 015815 (single transgenic line)
  2. The Jackson Lab: Stock# 024854 (double transgenic line)

Further Reading


  1. . Tau causes synapse loss without disrupting calcium homeostasis in the rTg4510 model of tauopathy. PLoS One. 2013;8(11):e80834. Epub 2013 Nov 20 PubMed.
  2. . Effects of the C57BL/6 strain background on tauopathy progression in the rTg4510 mouse model. Mol Neurodegener. 2014 Jan 15;9:8. PubMed.
  3. . Pathogenic tau species drive a psychosis-like phenotype in a mouse model of Alzheimer's disease. Behav Brain Res. 2014 Dec 15;275:27-33. Epub 2014 Aug 20 PubMed.
  4. . Age-dependent neurofibrillary tangle formation, neuron loss, and memory impairment in a mouse model of human tauopathy (P301L). J Neurosci. 2005 Nov 16;25(46):10637-47. PubMed.
  5. . Region-specific dissociation of neuronal loss and neurofibrillary pathology in a mouse model of tauopathy. Am J Pathol. 2006 May;168(5):1598-607. PubMed.
  6. . Sex difference in pathology and memory decline in rTg4510 mouse model of tauopathy. Neurobiol Aging. 2011 Apr;32(4):590-603. Epub 2009 May 7 PubMed.
  7. . Homeostatic responses by surviving cortical pyramidal cells in neurodegenerative tauopathy. Acta Neuropathol. 2011 Nov;122(5):551-64. PubMed.
  8. . Fractalkine overexpression suppresses tau pathology in a mouse model of tauopathy. Neurobiol Aging. 2013 Jun;34(6):1540-8. PubMed.
  9. . Synaptic alterations in the rTg4510 mouse model of tauopathy. J Comp Neurol. 2012 Oct 10; PubMed.
  10. . Effects of the C57BL/6 strain background on tauopathy progression in the rTg4510 mouse model. Mol Neurodegener. 2014 Jan 15;9:8. PubMed.
  11. . Characteristics of TBS-Extractable Hyperphosphorylated Tau Species: Aggregation Intermediates in rTg4510 Mouse Brain. J Alzheimers Dis. 2012 Aug 31; PubMed.