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01.12.2014 | Research article | Ausgabe 1/2014 Open Access

Molecular Neurodegeneration 1/2014

Motor and cognitive deficits in aged tau knockout mice in two background strains

Zeitschrift:
Molecular Neurodegeneration > Ausgabe 1/2014
Autoren:
Peng Lei, Scott Ayton, Steve Moon, Qihao Zhang, Irene Volitakis, David I Finkelstein, Ashley I Bush
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1750-1326-9-29) contains supplementary material, which is available to authorized users.

Competing interests

Dr Finkelstein is a shareholder in and paid scientific consultants for Prana Biotechnology Pty Ltd. Dr. Bush is a shareholder in Prana Biotechnology Pty Ltd., Eucalyptus Pty Ltd., Mesoblast Pty Ltd. and a paid consultant for Collaborative Medicinal Developments LLC and Brighton Biotech LLC.

Authors’ contributions

Scientific concept: PL, AIB. Experimental design: PL, SA, DIF, AIB. Experiments: PL, SA, SM, QZ, IV. Manuscript preparation: PL, AIB. Manuscript edit: all authors. All authors read and approved the final manuscript.

Abstract

Background

We recently reported that Parkinsonian and dementia phenotypes emerge between 7-12 months of age in tau-/- mice on a Bl6/129sv mixed background. These observations were partially replicated by another group using pure Bl6 background tau-/- mice, but notably they did not observe a cognitive phenotype. A third group using Bl6 background tau-/- mice found cognitive impairment at 20-months of age.

Results

To reconcile the observations, here we considered the genetic, dietary and environmental variables in both studies, and performed an extended set of behavioral studies on 12-month old tau+/+, tau+/-, and tau-/- mice comparing Bl6/129sv to Bl6 backgrounds. We found that tau-/- in both backgrounds exhibited reduced tyrosine hydroxylase-positive nigral neuron and impaired motor function in all assays used, which was ameliorated by oral treatment with L-DOPA, and not confounded by changes in body weight. Tau-/- in the C57BL6/SV129 background exhibited deficits in the Y-maze cognition task, but the mice on the Bl6 background did not.

Conclusions

These results validate our previous report on the neurodegenerative phenotypes of aged tau-/- mice, and show that genetic background may impact the extent of cognitive impairment in these mice. Therefore excessive lowering of tau should be avoided in therapeutic strategies for AD.
Zusatzmaterial
Additional file 1: Figure S1.: No correlation between weight and Rotarod test performance in 12-month-old mice. (PDF 80 KB)
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Additional file 2: Figure S2.: No correlation between weight and Pole test performance in 12-month-old mice. (PDF 78 KB)
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Additional file 3: Figure S3.: Temporal Open field profile. (PDF 215 KB)
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Additional file 4: Figure S4.: Analysis on 10 mins movement in Open field test. (PDF 115 KB)
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Additional file 5: Figure S5.: Additional parameters analyzed by Digigait apparatus. (PDF 152 KB)
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Additional file 6: Table S1.: Mouse number and gender used in each experiment. (PDF 73 KB)
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Authors’ original file for figure 1
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Authors’ original file for figure 2
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Authors’ original file for figure 3
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Authors’ original file for figure 4
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Authors’ original file for figure 5
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Authors’ original file for figure 6
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Authors’ original file for figure 7
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Authors’ original file for figure 8
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Literatur
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