Updated 16 January 2009

General Information

Transgene: A transgene including a cDNA of the shortest human tau isoform (T44, also known as fetal tau) driven by the mouse PrP promoter and 3' untranslated sequences was used to create tau Tg mice on a B6D2/F1 background.

Mutation: Human Tau

Promoter: MoPrP

Mouse Strain: B6D2-Tg(Prnp-MAPT)43Vle/J

Phenotype

Neuropathological Analysis:

The heterozygous Tg mouse line 43 overexpresses human tau proteins at levels approximately 10 fold higher than endogenous mouse tau. 3- to 12-month-old Tg mice accumulate insoluble intraneuronal filamentous hyperphosphorylated tau inclusions accompanied by neurodegeneration in the spinal cord. NFT-like inclusions were first detected in Tg mice at 18 to 20 months of age and they were detected by Congo red, Thioflavin S. Observed progressive, age-dependent accumulation of argyrophilic, tau-immunoreactive inclusions in neurons of spinal cord, brainstem, and neocortex, similar to human tauopathies. Mice suffer progressive, age-dependant neuronal damage, motor weakness and gliosis.

Behavioral:

Homozygous mice died in utero or within 3 months postnatal. Progressive motor weakness, impaired ability to stand on a slanted surface.

Availability

The Jackson Lab
See Jax Datasheet: #003741

Patents:

References

Primary:

Ishihara T, Hong M, Zhang B, Nakagawa Y, Lee MK, Trojanowski JQ, Lee VM-Y. Age-Dependent Emergence and Progression of a Tauopathy in Transgenic Mice Overexpressing the Shortest Human Tau Isoform. Neuron 24:751-762, 1999. Abstract.

Associated:

Ishihara T, Zhang B, Higuchi M, Yoshiyama Y, Trojanowski JQ, Lee V M-Y. Age-Dependent Induction of Congophilic Neurofibrillary Tau Inclusions in Tau Transgenic Mice. Am J Pathology 158:555-562, 2001. Abstract.

Ishihara T, Higuchi M, Zhang B, Yoshiyama Y, Hong M, Trojanowski JQ, Lee VM. Attenuated neurodegenerative disease phenotype in tau transgenic mouse lacking neurofilaments. J Neurosci. 2001 Aug 15;21(16):6026-35. Abstract.

Nakashima H, Ishihara T, Yokota O, Terada S, Trojanowski JQ, Lee VM, Kuroda S. 2004. Effects of alpha-tocopherol on an animal model of tauopathies. Free Radic Biol Med. 37 :176-86. Abstract.

Zhang B, Maiti A, Shively S, Lakhani F, Mcdonald-Jones, G, Bruce J, Lee EB, Xie SX, Joyce S, Li C, Toleikis PM, Lee VMY, Trojanowshi JQ. Microtubule-binding drugs offset tau sequestration by stabilizing microtubules and reversing fast axonal transport deficits in a tauopathy model. Proc Natl Acad Sci U S A 102 (1); 227-231, 2005. Abstract.

Yoshiyama Y, Uryu K, Higuchi M, Longhi L, Hoover R, Fujimoto S, McIntosh T, Lee VM, Trojanowski JQ. Enhanced neurofibrillary tangle formation, cerebral atrophy, and cognitive deficits induced by repetitive mild brain injury in a transgenic tauopathy mouse model. J Neurotrauma. 2005 Oct;22(10):1134-41. Abstract .