Mutations: MAPT V337M (Seattle Family A)
Modification: MAPT: Transgenic
Disease Relevance: Alzheimer's Disease, Frontotemporal Dementia
Strain Name: N/A
Genetic Background: B6SJL/F1
Human 4-repeat tau driven by the PDGF-β promoter. Tagged with myc and Flag on the N- and C-terminals respectively.
SDS-insoluble tau aggregates in hippocampus. Degenerating neurons in the hippocampus containing phosphorylated and ubiquitinated tau aggregates with β-sheet structure (Tanemura et al., 2002).
Higher overall spontaneous locomotion than non-transgenic littermates in elevated plus maze. No differences in the Morris water maze (Tanemura et al., 2002).
The amount of mutant tau varied, but was generally less than one tenth of endogenous tau levels (Tanemura et al., 2001). In hippocampal slices there was attenuation of the Schaffer collateral-evoked neural response (Tanemura et al., 2002).
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
- Synaptic Loss
Fibrillar staining in the hippocampus of 11 month old animals by Congo red birefringence. Absent in 4 month old mice, indicating the formation of these neurofilament-like structures occurs between 4 and 11 months (Tanemura et al., 2001).
Evidence of hippocampal neuronal degeneration in 10 month old animals: irregularly shaped neurons with tau pathology that stained with propidium iodide. As characteristics of apoptosis were not observed, the neurons were thought to be undergoing non-apoptotic atrophic degeneration (Tanemura et al., 2002).
Changes in LTP/LTD
In hippocampal slices there was an attenuation of the amplitude of Schaffer collateral evoked hippocampal depolarization (Tanemura et al., 2002).
Behavioral abnormalities measured in 11 month-old mice. They spent more time in the open arms of the elevated plus maze and had greater overall locomoter activity. No differences in the Morris water maze compared with non-transgenic mice, suggesting the transgenic animals retain spatial recognition abilities (Tanemura et al., 2002).
- 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. 2002 Jan 1;22(1):133-41. PubMed.
- 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. PubMed.