DRPLA transgenic mouse substrains carrying single copy of full-length mutant human DRPLA gene with variable sizes of expanded CAG repeats exhibit CAG repeat length- and age-dependent changes in behavioral abnormalities and gene expression profiles

2012 ◽  
Vol 46 (2) ◽  
pp. 336-350 ◽  
Author(s):  
Kazushi Suzuki ◽  
Jiayi Zhou ◽  
Toshiya Sato ◽  
Keizo Takao ◽  
Tsuyoshi Miyagawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgenic Mouse ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Single Copy ◽  
Repeat Length ◽  
Cag Repeat ◽  
Cag Repeats ◽  
Behavioral Abnormalities ◽  
Age Dependent

scholarly journals Integrated analysis of the aging brain transcriptome and proteome in tauopathy

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Carl Grant Mangleburg ◽  
Timothy Wu ◽  
Hari K. Yalamanchili ◽  
Caiwei Guo ◽  
Yi-Chen Hsieh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Mutant Form ◽  
Brain Gene Expression ◽  
Brain Transcriptome ◽  
Age Dependent

Abstract Background Tau neurofibrillary tangle pathology characterizes Alzheimer’s disease and other neurodegenerative tauopathies. Brain gene expression profiles can reveal mechanisms; however, few studies have systematically examined both the transcriptome and proteome or differentiated Tau- versus age-dependent changes. Methods Paired, longitudinal RNA-sequencing and mass-spectrometry were performed in a Drosophila model of tauopathy, based on pan-neuronal expression of human wildtype Tau (TauWT) or a mutant form causing frontotemporal dementia (TauR406W). Tau-induced, differentially expressed transcripts and proteins were examined cross-sectionally or using linear regression and adjusting for age. Hierarchical clustering was performed to highlight network perturbations, and we examined overlaps with human brain gene expression profiles in tauopathy. Results TauWT induced 1514 and 213 differentially expressed transcripts and proteins, respectively. TauR406W had a substantially greater impact, causing changes in 5494 transcripts and 697 proteins. There was a ~ 70% overlap between age- and Tau-induced changes and our analyses reveal pervasive bi-directional interactions. Strikingly, 42% of Tau-induced transcripts were discordant in the proteome, showing opposite direction of change. Tau-responsive gene expression networks strongly implicate innate immune activation. Cross-species analyses pinpoint human brain gene perturbations specifically triggered by Tau pathology and/or aging, and further differentiate between disease amplifying and protective changes. Conclusions Our results comprise a powerful, cross-species functional genomics resource for tauopathy, revealing Tau-mediated disruption of gene expression, including dynamic, age-dependent interactions between the brain transcriptome and proteome.

scholarly journals Single-nucleus RNA-seq identifies Huntington disease astrocyte states

2019 ◽  
Author(s):  
Osama Al-Dalahmah ◽  
Alexander A Sosunov ◽  
A Shaik ◽  
Kenneth Ofori ◽  
Yang Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Huntington Disease ◽  
Expression Profiles ◽  
Lipid Synthesis ◽  
Gene Expression Profiles ◽  
Cag Repeats ◽  
Cell Gene Expression ◽  
Single Nucleus ◽  
Cell Gene

AbstractHuntington Disease (HD) is an inherited movement disorder caused by expanded CAG repeats in the Huntingtin gene. We have used single nucleus RNASeq (snRNASeq) to uncover cellular phenotypes that change in the disease, investigating single cell gene expression in cingulate cortex of patients with HD and comparing the gene expression to that of patients with no neurological disease. In this study, we focused on astrocytes, although we found significant gene expression differences in neurons, oligodendrocytes, and microglia as well. In particular, the gene expression profiles of astrocytes in HD showed multiple signatures, varying in phenotype from cells that had markedly upregulated metallothionein and heat shock genes, but had not completely lost the expression of genes associated with normal protoplasmic astrocytes, to astrocytes that had substantially upregulated GFAP and had lost expression of many normal protoplasmic astrocyte genes as well as metallothionein genes. When compared to astrocytes in control samples, astrocyte signatures in HD also showed downregulated expression of a number of genes, including several associated with protoplasmic astrocyte function and lipid synthesis. Thus, HD astrocytes appeared in variable transcriptional phenotypes, and could be divided into several different “states”, defined by patterns of gene expression. Ultimately, this study begins to fill the knowledge gap of single cell gene expression in HD and provide a more detailed understanding of the variation in changes in gene expression during astrocyte “reactions” to the disease.

scholarly journals Gene expression profiles complement the analysis of genomic modifiers of the clinical onset of Huntington disease

2019 ◽  
Author(s):  
Galen E.B. Wright ◽  
Nicholas S. Caron ◽  
Bernard Ng ◽  
Lorenzo Casal ◽  
Xiaohong Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Huntington Disease ◽  
Neurodegenerative Disorder ◽  
Age Of Onset ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cag Repeat ◽  
Biologically Relevant ◽  
Clinical Onset ◽  
Genome Wide Data

ABSTRACTHuntington disease (HD) is a neurodegenerative disorder that is caused by a CAG repeat expansion in the HTT gene. In an attempt to identify genomic modifiers that contribute towards the age of onset of HD, we performed a transcriptome wide association study assessing heritable differences in genetically determined expression in diverse tissues, employing genome wide data from over 4,000 patients. This identified genes that showed evidence for colocalization and replication, with downstream functional validation being performed in isogenic HD stem cells and patient brains. Enrichment analyses detected associations with various biologically-relevant gene sets and striatal coexpression modules that are mediated by CAG length. Further, cortical coexpression modules that are relevant for HD onset were also associated with cognitive decline and HD-related traits in a longitudinal cohort. In summary, the combination of population-scale gene expression information with HD patient genomic data identified novel modifier genes for the disorder.

scholarly journals Integrated analysis of the aging brain transcriptome and proteome in tauopathy

2020 ◽  
Author(s):  
Carl Grant Mangleburg ◽  
Timothy Wu ◽  
Hari K. Yalamanchili ◽  
Caiwei Guo ◽  
Yi-Chen Hsieh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Integrated Analysis ◽  
Aging Brain ◽  
Brain Gene Expression ◽  
Brain Transcriptome ◽  
Age Dependent

AbstractBackgroundTau neurofibrillary tangle pathology characterizes Alzheimer’s disease and other neurodegenerative tauopathies. Brain gene expression profiles can reveal mechanisms; however, few studies have systematically examined both the transcriptome and proteome or differentiated Tau- versus age-dependent changes.MethodsPaired, longitudinal RNA-sequencing and mass-spectrometry were performed in a Drosophila model of tauopathy, based on pan-neuronal expression of human wildtype Tau (TauWT) or a mutation causing frontotemporal dementia (TauR406W). Tau-induced, differentially expressed transcripts and proteins were examined cross-sectionally or using linear regression and adjusting for age. Hierarchical clustering was performed to highlight network perturbations, and we examined overlaps with human brain gene expression profiles in tauopathy.ResultsTauWT induced 1,514 and 213 differentially expressed transcripts and proteins, respectively. TauR406W had a substantially greater impact, causing changes in 5,494 transcripts and 697 proteins. There was a ~70% overlap between age- and Tau-induced changes and our analyses reveal pervasive bi-directional interactions. Strikingly, 42% of Tau-induced transcripts were discordant in the proteome, showing opposite direction of change. Tau-responsive gene expression networks strongly implicate innate immune activation, despite the absence of microglia in flies. Cross-species analyses pinpoint human brain gene perturbations specifically triggered by Tau pathology and/or aging, and further differentiate between disease amplifying and protective changes.ConclusionsOur results comprise a powerful, cross-species functional genomics resource for tauopathy, revealing Tau-mediated disruption of gene expression, including dynamic, age-dependent interactions between the brain transcriptome and proteome.

scholarly journals Long-Term Oral Administration of LLHK, LHK, and HK Alters Gene Expression Profile and Restores Age-Dependent Atrophy and Dysfunction of Rat Salivary Glands

Biomedicines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 38
Author(s):  
Yasuko Ishikawa ◽  
Tomasz D Pieczonka ◽  
Aneta M Bragiel-Pieczonka ◽  
Harumichi Seta ◽  
Tadahiro Ohkuri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Oral Administration ◽  
Salivary Glands ◽  
Expression Profiles ◽  
Functional Decline ◽  
Gene Expression Profiles ◽  
Salivary Secretion ◽  
Salivary Protein ◽  
Age Dependent

Xerostomia, also known as dry mouth, is caused by a reduction in salivary secretion and by changes in the composition of saliva associated with the malfunction of salivary glands. Xerostomia decreases quality of life. In the present study, we investigated the effects of peptides derived from β-lactoglobulin C on age-dependent atrophy, gene expression profiles, and the dysfunction of salivary glands. Long-term oral administration of Leu57-Leu58-His59-Lys60 (LLHK), Leu58-His59-Lys60 (LHK) and His59-Lys60 (HK) peptides induced salivary secretion and prevented and/or reversed the age-dependent atrophy of salivary glands in older rats. The transcripts of 78 genes were upregulated and those of 81 genes were downregulated by more than 2.0-fold (p ≤ 0.05) after LHK treatment. LHK upregulated major salivary protein genes such as proline-rich proteins (Prpmp5, Prb3, Prp2, Prb1, Prp15), cystatins (Cst5, Cyss, Vegp2), amylases (Amy1a, Amy2a3), and lysozyme (Lyzl1), suggesting that LLHK, LHK, and HK restored normal salivary function. The AP-2 transcription factor gene (Tcfap2b) was also induced significantly by LHK treatment. These results suggest that LLHK, LHK, and HK-administration may prevent and/or reverse the age-dependent atrophy and functional decline of salivary glands by affecting gene expression.

scholarly journals Global expression profiles from C57BL/6J and DBA/2J mouse lungs to determine aging-related genes

2007 ◽  
Vol 31 (3) ◽  
pp. 429-440 ◽  
Author(s):  
Vikas Misra ◽  
Hannah Lee ◽  
Anju Singh ◽  
Kewu Huang ◽  
Rajesh K. Thimmulappa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Structural Integrity ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Accelerated Aging ◽  
Mouse Strains ◽  
Xenobiotic Detoxification ◽  
Age Dependent ◽  
The Matrix ◽  
And Function

This study identified gene expression profiles that provided evidence for genomic mechanisms underlying the pathophysiology of aging lung. Aging lungs from C57BL/6 (B6) and DBA/2 (D2) mouse strains differ in physiology and morphometry. Lungs were harvested from B6 mice at 2, 18, and 26 mo and from D2 mice at 2 and 18 mo of age. Purified RNA was subjected to oligonucleotide microarray analyses, and differential expression analyses were performed for comparison of various data sets. A significant majority of differentially expressed genes were upregulated with aging in both strains. Aging D2 lungs uniquely exhibited upregulation in stress-response genes including xenobiotic detoxification cascades. In contrast, aging B6 lungs showed downregulation of heat shock-response genes. Age-dependent downregulation of genes common to both B6 and D2 strains included several collagen genes (e.g., Col1a1 and Col3a1). There was a greater elastin gene ( Eln) expression in D2 mice at 2 mo, and Eln was uniquely downregulated with age in this strain. The matrix metalloproteinase 14 gene ( Mmp14), critical to alveolar structural integrity, was also downregulated with aging in D2 mice only. Several polymorphisms in the regulatory and untranslated regions of Mmp14 were identified between strains, suggesting that variation in Mmp14 gene regulation contributes to accelerated aging of lungs in D2 mice. In summary, lungs of B6 and D2 mice age with variable rates at the gene expression level, and these quantifiable genomic differences provide a template for understanding the variability in age-dependent changes in lung structure and function.

scholarly journals Consistent gene expression profiles in MexTAg transgenic mouse and wild type mouse asbestos-induced mesothelioma

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Cleo Robinson ◽  
Ian M. Dick ◽  
Michael J. Wise ◽  
Andrew Holloway ◽  
Dileepa Diyagama ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgenic Mouse ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Wild Type Mouse ◽  
Wild Type

1327: Gene Expression Profiles in Benign Prostatic Hyperplasia

2004 ◽  
Vol 171 (4S) ◽  
pp. 349-350
Author(s):  
Gaelle Fromont ◽  
Michel Vidaud ◽  
Alain Latil ◽  
Guy Vallancien ◽  
Pierre Validire ◽  
...  
Keyword(s):  
Gene Expression ◽  
Benign Prostatic Hyperplasia ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Prostatic Hyperplasia
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