Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA205896 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We intend to screen altered genes after overexpression of miR-196a in HD transgenic mice. Two transgenic mouse lines were used in this study, including HD transgenic mice and HD transgenic mice overexpressing miR-196a. The mice were all at approximate 12 months of age. At this point, HD transgenic mice showed severve motor dysfunctions, whereas HD transgenic mice overexpressing miR-196a displayed mild motor dysfunctions.
2013-05-30 | GSE47500 | GEO
Project description:We intend to screen altered genes after overexpression of miR-196a in HD transgenic mice. Two transgenic mouse lines were used in this study, including HD transgenic mice and HD transgenic mice overexpressing miR-196a. The mice were all at approximate 12 months of age. At this point, HD transgenic mice showed severve motor dysfunctions, whereas HD transgenic mice overexpressing miR-196a displayed mild motor dysfunctions. We used the striatum tissues from 2 HD transgenic mice and 3 HD transgenic mice overexpressing miR-196a. The mice were all at approximate 12 months of age. Two technique repeats were performed for each sample.
2013-05-30 | E-GEOD-47500 | biostudies-arrayexpress
Project description:BACKGROUND MicroRNAs (miRNAs) are small non-coding RNAs that recognize sites of complementarity of target messenger RNAs, resulting in transcriptional regulation and translational repression of target genes. In Huntington’s disease (HD), a neurodegenerative disease caused by a trinucleotide repeat expansion, miRNA dyregulation has been reported, which may impact gene expression and modify the progression and severity of HD. METHODS: We performed next-generation miRNA sequence analysis in prefrontal cortex (Brodmann Area 9) from 26 HD, 2 asymptomatic HD, and 36 control brains. Neuropathological information was available for all HD brains, including age at disease onset, CAG-repeat size, Vonsattel grade, and Hadzi-Vonsattel striatal and cortical scores, a continuous measure of the extent of neurodegeneration. Linear models were performed to examine the relationship of miRNA expression to these clinical features, and messenger RNA targets of associated miRNAs were tested for gene ontology term enrichment. RESULTS: We identified 75 miRNAs differentially expressed in HD brain (FDR q-value <0.05). Among the HD brains, nine miRNAs were significantly associated with Vonsattel grade of neuropathological involvement and three of these, miR-10b-5p, miR-10b-3p, and miR-302a-3p, significantly related to the Hadzi-Vonsattel striatal score (a continuous measure of striatal involvement) after adjustment for CAG length. Five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-10b-3p, and miR-106a-5p) were identified as having a significant relationship to CAG length-adjusted age of onset including miR-10b-5p, the mostly strongly over-expressed miRNA in HD cases. Although prefrontal cortex was the source of tissue profiled in these studies, the relationship of miR-10b-5p expression to striatal involvement in the disease was independent of cortical involvement. Correlation of miRNAs to the clinical features clustered by direction of effect and the gene targets of the observed miRNAs showed association to processes relating to nervous system development and transcriptional regulation. CONCLUSIONS: These results demonstrate that miRNA expression in cortical BA9 provides insight into striatal involvement and support a role for these miRNAs, particularly miR-10b-5p, in HD pathogenicity. The miRNAs identified in our studies of postmortem brain tissue may be detectable in peripheral fluids and thus warrant consideration as accessible biomarkers for disease stage, rate of progression, and other important clinical characteristics of HD. 26 Huntington's disease, 2 asymptomatic HD gene positive and 49 neurologically normal control prefrontal cortex samples
2015-03-12 | E-GEOD-64977 | biostudies-arrayexpress
Project description:Dysregulation of the kynurenine (Kyn) pathway has been associated with the progression of Huntington's disease (HD). In particular, elevated levels of the kynurenine metabolites 3-hydroxy kynurenine (3-OH-Kyn) and quinolinic acid (Quin), have been reported in the brains of HD patients as well as in rodent models of HD. The production of these metabolites is controlled by the activity of kynurenine mono-oxygenase (KMO), a mitochondrial outer membrane enzyme which catalyzes the synthesis of 3-OH-Kyn from Kyn. Thus inhibiting KMO is expected to produce a beneficial effect in Huntington's Disease (HD) patients, hopefully reversing their phenotype to match healthy subjects. To test this effect, we acutely treated a mouse model of HD (R6/2, a transgenic mouse model of HD which contains a human HTT gene containing 90 CAG repeats) and wild type mice with a KMO inhibitor, and separately used a mock treatment on both the transgenic mice and wild type mice. The goal of this project is to analyze the RNA-seq data and find gene expression changes associated with the KMO inhibitor
2017-10-30 | GSE106161 | GEO
Project description:Dysregulation of the kynurenine (Kyn) pathway has been associated with the progression of Huntington's disease (HD). In particular, elevated levels of the kynurenine metabolites 3-hydroxy kynurenine (3-OH-Kyn) and quinolinic acid (Quin), have been reported in the brains of HD patients as well as in rodent models of HD. The production of these metabolites is controlled by the activity of kynurenine mono-oxygenase (KMO), a mitochondrial outer membrane enzyme which catalyzes the synthesis of 3-OH-Kyn from Kyn. Thus inhibiting KMO is expected to produce a beneficial effect in Huntington's Disease (HD) patients, hopefully reversing their phenotype to match healthy subjects. To test this effect, we chronically treated a mouse model of HD (R6/2, a transgenic mouse model of HD which contains a human HTT gene containing 90 CAG repeats) and wild type mice with a KMO inhibitor for 8 weeks, and separately used a mock treatment on both the transgenic mice and wild type mice. The goal of this project is to analyze the RNA-seq data and find gene expression changes associated with the KMO inhibitor.
2017-10-30 | GSE105158 | GEO
Project description:Huntington's disease (HD) is a dominantly inherited genetic disease caused by mutant huntingtin (htt) protein with expanded polyglutamine tracts. A neuropathological hallmark of HD is the presence of neuronal inclusions of mutant htt. p62 is an important regulatory protein in selective autophagy, a process by which aggregated proteins are degraded, and it is associated with several neurodegenerative disorders including HD. Here we investigated the effect of p62 depletion in three HD model mice: R6/2, HD190QG and HD120QG mice. We found that loss of p62 in these models led to longer lifespans and reduced nuclear inclusions, although cytoplasmic inclusions increased with polyglutamine length. In mouse embryonic fibroblasts (MEFs) with or without p62, mutant htt with a nuclear localization signal (NLS) showed no difference in nuclear inclusion between the two MEF types. In the case of mutant htt without NLS, however, p62 depletion increased cytoplasmic inclusions. Furthermore, to examine the effect of impaired autophagy in HD model mice, we crossed R6/2 mice with Atg5 conditional knockout mice. These mice also showed decreased nuclear inclusions and increased cytoplasmic inclusions, similar to HD mice lacking p62. These data suggest that the genetic ablation of p62 in HD model mice enhances cytoplasmic inclusion formation by interrupting autophagic clearance of polyQ inclusions. This reduces polyQ nuclear influx and paradoxically ameliorates disease phenotypes by decreasing toxic nuclear inclusions. Gene expression profiles were analyzed to examine the effects of p62 depletion in mouse with or without mutant huntingtin exon 1 To examine the effect of p62 depletion on the transcriptome of Huntington's disease model mice, we crossed p62 knockout mice with HD model mice. We extracted total RNA from the striatum of these mice at 8 weeks and used for a microaaray analysis. The samples are HD transgenic mice with p62 knockout (HD_p62KO), HD mice with normal p62 (HD_p62WT), non-HD-transgenic mice with p62 knockout (NT_p62KO), and non-HD-transgenic mice with normal p62 (NT_p62WT).
2014-10-10 | E-GEOD-62210 | biostudies-arrayexpress
Project description:The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington's disease transgenic mice
| PRJNA136765 | ENA
Project description:N17 Modifies Mutant Huntingtin Nuclear Pathogenesis and Severity of Disease in HD BAC Transgenic Mice
| PRJNA270867 | ENA
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
2014-12-04 | GSE61417 | GEO
Project description:Allelic Series of Huntington's Disease Knock-in Mice Reveals Expression Discorrelates
| PRJNA297794 | ENA