Posted 7 October 2002

General Information

Transgene: Human longest tau cDNA

Mutation: V337M causing frontotemporal dementia parkinsonism-17 (FTDP-17)

Promoter: PDGF-beta promoter

Mouse Strain: B6SJL

Phenotype

Neuropathological Analysis:

SDS-insoluble tau aggregates found in hippocampus.

Under light microscopy, neurons of irregular shape in hippocampus were immunoreactive for paired helical filament-associated tau (as visualized by Alz-50); exhibited Congo Red birefringence; and accumulated RNA.

Under electron microscopy, irregularly shaped neurons failed to show signs of apoptotic cells death, instead showing signs of atrophic cell death ("dark cell degeneration:): atrophy of both nucleus and cytoplasm with accumulations of phosphorylated tau, increased number of ribosomes, disappearence of microtubules, and deposition of tau fibrils.

Neurophysiological:

In hippocampal slice preparation, there was attentuation of the Schaffer collateral-evoked neural response.

Behavioral:

Tg mice showed higher overall spontaneous locomotion than non-Tg littermates throughout testing in elevated plus maze. There were no differences in the Morris water maze.

Availability

Patents: None

Reference

Tanemura K, Murayama M, Akagi T, Hashikawa T, Tominaga T, Ichikawa M, Yamaguchi H, Takashima A. Neurodegeneration with tau accumulation in a transgenic mouse expressing V337M human tau. J Neurosci. 1 Jan 2002;22(1):133–141. Abstract.

Tanemura K, Akagi T, Murayama M, Kikuchi N, Murayama O, Hashikawa T, Yoshiike Y, Park JM, Matsuda K, Nakao S, Sun X, Sato S, Yamaguchi H, Takashima A. Formation of filamentous tau aggregations in transgenic mice expressing V337M human tau. Neurobiol Dis 2001 Dec;8(6):1036-45.Abstract.