Gene expression profiling of the tau mutant (P301L) transgenic mouse brain

Ho, Lap; Xiang, Zhou; Mukherjee, Piali; Zhang, Wen; Jesus, Nidia De; Mirjany, Mana; Yemul, Shrishailam; Pasinetti, Giulio Maria

doi:10.1016/s0304-3940(01)02044-4

Cited by 26 publications

(10 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compared to mRNA changes reported to be caused by tau overexpression in tau transgenic mice (Chen et al, 2004; Ho et al, 2001), we found more changes, and of greater amplitude, in the course of two weeks of tau expression in rats. The genes reported from the tau transgenic mice did not appear on our lists, although differences in a number of factors, including the time-course, the host species, the genotype of tau, and the brain region collected could have contributed.…”

Section: Resultscontrasting

confidence: 77%

Transcriptome analysis of a tau overexpression model in rats implicates an early pro-inflammatory response

Wang

Dayton

Zweig

et al. 2010

Experimental Neurology

View full text Add to dashboard Cite

Neurofibrillary tangles comprised of the microtubule-associated protein tau are pathological features of Alzheimer's disease and several other neurodegenerative diseases, such as progressive supranuclear palsy. We previously overexpressed tau in the substantia nigra of rats and mimicked some of the neurodegenerative sequelae that occur in humans such as tangle formation, loss of dopamine neurons, and microgliosis. To study molecular changes involved in the tau-induced disease state, we used DNA microarrays at an early stage of the disease process. A range of adeno-associated virus (AAV9) vector doses for tau were injected in groups of rats with a survival interval of two weeks. Specific decreases in messages for dopamine related genes validated the technique with respect to the dopaminergic cell loss observed. Of the mRNAs upregulated, there was a dose-dependent effect on multiple genes involved in immune response such as chemokines, interferon-inducible genes and leukocyte markers, only in the tau vector groups and not in dose-matched controls of either transgene-less empty vector or control green fluorescent protein vector. Histological staining for dopamine neurons and microglia matched the loss of dopaminergic markers and upregulation of immune response mRNAs in the microarray data, respectively. RT-PCR for selected markers confirmed the microarray results, with similar changes found by either technique. The mRNA data correlate well with previous findings, and underscore microgliosis and immune response in the degenerative process following tau overexpression.

show abstract

Section: Resultscontrasting

confidence: 77%

Transcriptome analysis of a tau overexpression model in rats implicates an early pro-inflammatory response

Wang

Dayton

Zweig

et al. 2010

Experimental Neurology

View full text Add to dashboard Cite

show abstract

“…When expressed in Drosophila, it is hyperphosphorylated but not aggregated into filaments [106]. Expression of 4L G272V, V337M, and P301L in transgenic mice showed increased tau phosphorylation and tau inclusions [107][108][109][110][111].…”

Section: Ftdp-17 Tau Mutationsmentioning

confidence: 99%

Mechanism of Tau-Induced Neurodegeneration in Alzheimer Disease and Related Tauopathies

Alonso¹,

Li²,

Grundke‐Iqbal³

et al. 2008

CAR

123

View full text Add to dashboard Cite

The accumulation of hyperphosphorylated tau is a common feature of several dementias. Tau is one of the brain microtubule-associated proteins. Here we discuss tau's function in microtubule assembly and stabilization and with regards to tau's interactions with other proteins, membranes, and DNA. We describe and analyze important posttranslational modifications: hyperphosphorylation, glycosylation, ubiquitination, glycation, polyamination, nitration, and truncation. We discuss how these post-translational modifications can alter tau's biological function and what is known about tau self-assembly, and we propose a mechanism of tau polymerization. We analyze the impact of natural mutations on tau that cause fronto-temporal dementia associated with chromosome 17 (FTDP-1 7). Finally, we consider whether tau accumulation or its conformational change is related to tau-induced neurodegeneration, and we propose a mechanism of neurodegeneration.

show abstract

“…P301S mice show motor symptoms, including severe partial paralysis of the hindlimbs as well as hyperphosphorylated tau aggregates in the brain and spinal cord, but no signs of apoptosis (Allen et al , 2002). On the other hand, P301L mice have increased levels of apoptosis(Götz et al , 2001, Ho et al , 2001). These mice also display motor deficits and NFTs in the brain and spinal cord, as well as deposits in glial cells(Lewis J, 2000, Götz et al , 2001).…”

Section: Tau Oligomeric Strainsmentioning

confidence: 99%

Potential mechanisms and implications for the formation of tau oligomeric strains

Gerson

Mudher

Kayed

2016

Critical Reviews in Biochemistry and Molecular Biology

View full text Add to dashboard Cite

The culmination of many years of increasing research into the toxicity of tau aggregation in neurodegenerative disease has led to the consensus that soluble, oligomeric forms of tau are likely the most toxic entities in disease. While tauopathies overlap in the presence of tau pathology, each disease has a unique combination of symptoms and pathological features, however, most study into tau has grouped tau oligomers and studied them as a homogenous population. Established evidence from the prion field combined with the most recent tau and amyloidogenic protein research suggests that tau is a prion-like protein, capable of seeding the spread of pathology throughout the brain. Thus, it is likely that tau may also form prion-like strains or diverse conformational structures that may differ by disease and underlie some of the differences in symptoms and pathology in neurodegenerative tauopathies. The development of techniques and new technology for the detection of tau oligomeric strains may therefore lead to more efficacious diagnostic and treatment strategies for neurodegenerative disease.

show abstract

Gene expression profiling of the tau mutant (P301L) transgenic mouse brain

Cited by 26 publications

References 18 publications

Transcriptome analysis of a tau overexpression model in rats implicates an early pro-inflammatory response

Transcriptome analysis of a tau overexpression model in rats implicates an early pro-inflammatory response

Mechanism of Tau-Induced Neurodegeneration in Alzheimer Disease and Related Tauopathies

Potential mechanisms and implications for the formation of tau oligomeric strains

Contact Info

Product

Resources

About