Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition
Recent studies on tauopathy animal models suggest that the concomitant expression of the endogenous murine tau delays the pathological accumulation of human tau, and interferes with the disease progression. To elucidate the role of endogenous murine tau in a model with both plaques and tangles, we d...
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doaj-2e1978d880a945a6ae992d34a6d1b1c92021-03-22T12:40:34ZengElsevierNeurobiology of Disease1095-953X2014-02-0162407415Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognitionDavid Baglietto-Vargas0Masashi Kitazawa1Elaine J. Le2Tatiana Estrada-Hernandez3Carlos J. Rodriguez-Ortiz4Rodrigo Medeiros5Kim N. Green6Frank M. LaFerla7Department of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697-4545, USADepartment of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697-4545, USA; Department of Molecular and Cell Biology, University of California, Merced, CA 95343, USADepartment of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697-4545, USADepartment of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697-4545, USADepartment of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697-4545, USA; Department of Molecular and Cell Biology, University of California, Merced, CA 95343, USADepartment of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697-4545, USADepartment of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697-4545, USADepartment of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA 92697-4545, USA; Corresponding author at: Department of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders (UCI MIND), 3212 Biological Sciences III, Irvine, CA 92697-4545, USA. Fax: +1 949 824 7356.Recent studies on tauopathy animal models suggest that the concomitant expression of the endogenous murine tau delays the pathological accumulation of human tau, and interferes with the disease progression. To elucidate the role of endogenous murine tau in a model with both plaques and tangles, we developed a novel transgenic mouse model by crossing 3xTg-AD with mtauKO mice (referred to as 3xTg-AD/mtauKO mice). Therefore, this new model allows us to determine the pathological consequences of the murine tau. Here, we show that 3xTg-AD/mtauKO mice have lower tau loads in both soluble and insoluble fractions, and lower tau hyperphosphorylation level in the soluble fraction relative to 3xTg-AD mice. In the 3xTg-AD model endogenous mouse tau is hyperphosphorylated and significantly co-aggregates with human tau. Despite the deletion of the endogenous tau gene in 3xTg-AD/mtauKO mice, cognitive dysfunction was equivalent to 3xTg-AD mice, as there was no additional impairment on a spatial memory task, and thus despite increased tau phosphorylation, accumulation and NFTs in 3xTg-AD mice no further effects on cognition are seen. These findings provide better understanding about the role of endogenous tau to Alzheimer's disease (AD) pathology and for developing new AD models.http://www.sciencedirect.com/science/article/pii/S0969996113002945Alzheimer's diseaseTauHippocampus3xTg-AD miceNeurofibrillary tangles |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
David Baglietto-Vargas Masashi Kitazawa Elaine J. Le Tatiana Estrada-Hernandez Carlos J. Rodriguez-Ortiz Rodrigo Medeiros Kim N. Green Frank M. LaFerla |
spellingShingle |
David Baglietto-Vargas Masashi Kitazawa Elaine J. Le Tatiana Estrada-Hernandez Carlos J. Rodriguez-Ortiz Rodrigo Medeiros Kim N. Green Frank M. LaFerla Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition Neurobiology of Disease Alzheimer's disease Tau Hippocampus 3xTg-AD mice Neurofibrillary tangles |
author_facet |
David Baglietto-Vargas Masashi Kitazawa Elaine J. Le Tatiana Estrada-Hernandez Carlos J. Rodriguez-Ortiz Rodrigo Medeiros Kim N. Green Frank M. LaFerla |
author_sort |
David Baglietto-Vargas |
title |
Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition |
title_short |
Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition |
title_full |
Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition |
title_fullStr |
Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition |
title_full_unstemmed |
Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition |
title_sort |
endogenous murine tau promotes neurofibrillary tangles in 3xtg-ad mice without affecting cognition |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2014-02-01 |
description |
Recent studies on tauopathy animal models suggest that the concomitant expression of the endogenous murine tau delays the pathological accumulation of human tau, and interferes with the disease progression. To elucidate the role of endogenous murine tau in a model with both plaques and tangles, we developed a novel transgenic mouse model by crossing 3xTg-AD with mtauKO mice (referred to as 3xTg-AD/mtauKO mice). Therefore, this new model allows us to determine the pathological consequences of the murine tau. Here, we show that 3xTg-AD/mtauKO mice have lower tau loads in both soluble and insoluble fractions, and lower tau hyperphosphorylation level in the soluble fraction relative to 3xTg-AD mice. In the 3xTg-AD model endogenous mouse tau is hyperphosphorylated and significantly co-aggregates with human tau. Despite the deletion of the endogenous tau gene in 3xTg-AD/mtauKO mice, cognitive dysfunction was equivalent to 3xTg-AD mice, as there was no additional impairment on a spatial memory task, and thus despite increased tau phosphorylation, accumulation and NFTs in 3xTg-AD mice no further effects on cognition are seen. These findings provide better understanding about the role of endogenous tau to Alzheimer's disease (AD) pathology and for developing new AD models. |
topic |
Alzheimer's disease Tau Hippocampus 3xTg-AD mice Neurofibrillary tangles |
url |
http://www.sciencedirect.com/science/article/pii/S0969996113002945 |
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