Transcriptomic analysis of RNA-sequencing data from nontransgenic and transgenic tau SPAM mice
Ontology highlight
ABSTRACT: We performed RNA-sequencing of nontransgenic and transgenic By line of tau SPAM mice (expressing the S320F/P301S aggregating mutations) at different ages of 2, 4, and 6 months. All of the samples were obtained from brain cortex.
Project description:Expression of PS19 Tau Transgenic mice from hippocampus at different ages 3, 6, 9, and 12 months We used Affy arrays to understand the global expression profile of PS19 Tau transgenic mice
Project description:Aggregation of the microtubule-associated protein, tau, can lead to neurofibrillary tangle formation in neurons and glia, the hallmark of tauopathy. The cellular damages induced by the tau overexpression and aggregation may lead to multiple pathologic features of tauopathy. However, the effect of aging on tauopathy has not been elucidated yet. Here, we conducted lncRNA/mRNA sequencing analysis on P301S mutant Tau transgenic mouse model (PS19) with different ages to track the genetic changes occurred by the aging and progression of tau overexpression.
Project description:We investigated the effects of human tau on subcellular populations of the brain mitochondrial proteome in vivo using transgenic htau mice at ages preceding (5 months) and coinciding with (8 months) onset of tauopathy.
Project description:To gain insight into the role of human APOE on tau-associated neurodegeneration, we examined P301S mutant tau transgenic mice carrying humanized APOE alleles
Project description:Many neurodegenerative disorders including Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) are characterized by abnormal protein deposition and frequently show comorbid pathology. Progranulin (PGRN) is implicated not only in TDP-43 but in tau and alpha-synuclein proteinopathies. However, the underlying mechanisms are unknown. Here, we generated P301S tau transgenic mice with PGRN haploinsufficiency and loss and found that those mice exhibit exacerbated disinhibition phenotype while showing attenuated memory impairment, hippocampal atrophy, and transcriptomic changes. Remarkably, the phenotypic alteration was accompanied by an increase in tau inclusions, which are positive for alpha-synuclein, a PGRN binding partner beta-glucocerebrosidase (GCase), and its substrate glucosylceramide. GCase inhibition or PGRN deficiency enhanced tau aggregation induced by AD-derived tau seeds in neurons. In vitro, GCase and glucosylceramide promoted P301S tau aggregation. Similar co-pathology was observed in AD and FTLD-GRN patients.
Project description:The purpose of this project was to compare whole genome expression in 5 transgenic mice with human genes for dementia that result in either plaques or tangle pathology to the expression in wild-type control mice and to each other at different stages of disease progression. Total RNA was obtained from hippocampus, cortex and cerebellum in four lines of ‘amyloid’ transgenic mice (mutant human APP and APP/PSEN1 genes) and ‘TAU’ transgenic mice (mutant human MAPT gene) as well as wild-type control mice at 8,16, 32 and 72 weeks