Background
Methods
Animals
Genotyping and genome-wide analysis of SNPs
Evaluation of disease-related symptoms in aged mice
Quantification of phosphorylated and total tau protein
Extraction of phosphorylated tau protein
Western blots
Trypsin digestion of sarkosyl-insoluble tau extracts
Isotropic fractionator
Immunohistochemistry
Homogenate and lysate preparation
Negative stain electron microscopy
Cell culture
Transduction of homogenates into clone 1 cells
Confocal analysis of seeded clone 1 cells
Data analysis
Results
Genetic profiles and tau expression in sublines of TgTauP301L mice
Neurologic symptoms and tau species in aged Tg mice
Quantification of neuronal loss in aged TgTauP301L mice
Heterogeneity in tau pathologies
aGenetic background (n ♀, ♂) |
bPathology Class average age in days ± SD (n♀, ♂) | ||||
---|---|---|---|---|---|
I | II | III | IV | V | |
C57BL/6Tac (16,12) |
c625 ± 90 (1,6) |
c633 ± 60 (7,2) |
c643 ± 77 (6,3) | 472, 567 (1,1) | 593 (1,0) |
129/SvEvTac (11,18) | 504, 662 (0,2) |
d666 ± 60 (5,7) |
d647 ± 61 (3,4) | 541 ± 56 (3,2) | 607 ± 73 (0,3) |
FVB/NJ (12,15) |
e583 ± 61 (2,8) |
e597 ± 59 (3,3) |
e615 ± 53 (5,2) | 602 ± 102 (2, 2) | N/A (0) |
Variable tau pathology versus transgene expression effects
Biochemical analyses of tau species in different pathology classes
Electron microscopic analysis of tau filaments
Mouse lines | Pathology Class I | Pathology Class II | Pathology Class IV | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Filament Types | Filament Types | Filament Types | ||||||||||
N | Straight Filament | Coiled Filament | Twisted Ribbon-like Filament | N | Straight Filament | Coiled Filament | Twisted Ribbon-like Filament | N | Straight Filament | Coiled Filament | Twisted Ribbon-like Filament | |
C57BL/6 | 2 | 39 | 35 | 1 | 2 | 189 | 0 | 0 | 2 | 6 | 0 | 0 |
52% | 47% | 1% | 100% | 0% | 0% | 100% | 0% | 0% | ||||
129SvEv | 1 | 22 | 0 | 1 | 1 | 55 | 0 | 0 | 3 | 23 | 0 | 0 |
96% | 0% | 4% | 100% | 0% | 0% | 100% | 0% | 0% | ||||
FVB/NJ | 2 | 21 | 0 | 0 | 3 | 121 | 1 | 0 | 3 | 14 | 0 | 0 |
100% | 0% | 0% | 99% | 1% | 0% | 100% | 0% | 0% |