Nonmutant (NM) 4-repeat (4R) human tau (rT1) mice have a Tet-responsive element (TRE or tetO) and mouse prion protein promoter sequences (PrP or Prnp) directing expression of the human microtubule-associated protein tau (MAPT) inserted into an intergenic site downstream of the Col1a1 locus. Mice homozygous for the rT1 allele are viable, fertility has not been assessed. rT1 mice were originally created as a control for rT2, the tau mutant with conditional (inducible/reversible) tauP301L expression (Stock No. <a href="https://www.jax.org/strain/032647"">032647</a>), however, induced rT1 mice exhibit an independent early phenotype that is pathogenic in postnatal development. When rT1 mice are exposed to tetracycline-controlled transactivator protein (tTA) or reverse tetracycline-controlled transactivator protein (rtTA), high levels of Tau in the resulting animals can be regulated with tetracycline or its analog doxycycline (dox). For example, breeding to Camk2a-tTA mice (see Stock Nos. <a href="https://www.jax.org/strain/003010">003010</a> / <a href="https://www.jax.org/strain/007004">007004</a>) results in progeny with conditional (inducible/reversible) tau expression in the forebrain. Induced rT1 mice exhibit elevated levels of human tau protein (12.6 fold vs. 6.2 fold) at 8 weeks of age as compared to the rT2 strain due to impaired degradation of hTau in the postsynaptic compartment. In addition, rT1 mice have higher phosphorylation levels on the tau protein. Five month old rT1 mice exhibit learning defects during visible platform training and deficits in spatial reference memory that are not found in rT2 mice. At 3-5 weeks of age, rT1 mice have reduced brain mass as compared to rT2 mice. The rT1 mice represent a model of tau expression in the forebrain and may be useful in the study of Alzheimer's disease.&nbsp;

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 Regulatable T1 (rT1) mice allow Tet-Off/Tet-On expression of the human microtubule-associated protein tau (MAPT) 4R isoform. These mice may be useful in generating animals with conditional (inducible/reversible) tau expression for studying the formation of neurofibrillary tangles associated with Alzheimer's disease, neurodegenerative tauopathies and frontotemporal dementia.

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