Updated 14 April 2003

General Information

Transgene:     Mtapt cDNAs provided by A. Andreadis

Mutation:     human P301L, wt 4 repeat tau containing exon 10 and lacking exons 2 and 3 (Wt4R)

Promoter: mouse prion promoter (MoPrP)

Mouse strain:     C57BL/DBA2/SW

Phenotype

Homozygous/heterozygous viability:     Both are viable

Relative Protein expression level to endogenous
Beta Amyloid: n/a
Presenilin: n/a
Tau:     hemizygous P301L and Wt4R expressed the transgenic tau at levels equivalent to that of the endogenous tau; homozygous P301L expressed human P301L tau at about twice the level observed in hemizygous mice.

Neurofibrillary tangles and neuronal loss in affected regions in brain and spinal cord.

Neuropathological Analysis:

Spinal cords of affected P301L mice showed fibrillary gliosis in the anterior horns, axonal degeneration in the anterior roots and axonal spheroids. Motor neurons in P301L showed a reduction of 48% in the spinal cord.

Neuronal lesions occurred in the amygdala, septal nuclei, pre-optic nuclei, hypothalamus, midbrain, pons, medulla, deep cerebellar nuclei and spinal cord. Distribution of the lesion is similar to some forms of FTDP-17

Morphologically heterogeneous tau-positive NFT appears in the diencephalon, brainstem, cerebellar nuclei and spinal cord.

Peripheral neuropathy and skeletal muscle with neurogenic atrophy

Wt4R mice up to 10 months of age lacked these neuropathological changes.

Behavioral:

Hang test: P301L mouse fell after grasping rope briefly whereas Wt4R and nontransgenic mice held with three limbs and tail without failing.

Severe motor and behavioral disturbances observed as early as 6.5 months in hemizygous and 4.5 months in homozygous P301L mice.

Also observed in P301L mice were appendicular weakness, delayed righting response, reduction in weight, grooming and vocalization, limb weakness, dystonic posturing and increase in docility

Crosses to create multigenic mouse: APP

Availability

Licensing/academic distribution contact information:

Taconic Farm
Available

Michael Hutton
Mayo Clinic Jacksonville
Jacksonville, Florida
Tel: 904-953-0159
Fax: 904-953-7370
Email: hutton.michael@mayo.edu

Patents: none

Reference

Primary:

Lewis J, McGowan E, Rockwood J, Melrose H, Nacharaju P, Van Slegtenhorst M, Gwinn-Hardy K, Paul Murphy M, Baker M, Yu X, Duff K, Hardy J, Corral A, Lin WL, Yen SH, Dickson DW, Davies P, Hutton M. Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat Genet 2000 Aug;25(4):402-5. Abstract .