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GSE61908
Mus musculus
11 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease caused by an expansion of a CAG repeat encoding a polyglutamine (PolyQ) tract in the Cav2.1 voltage-gated calcium channel. Pathologically, it is characterized by selective degeneration of cerebellar Purkinje cells (PCs), which are a common target for PolyQ-induced toxicity among several different SCAs. Mutant Cav2.1 confers toxicity mainly through a toxic gain-of-function mechanism, but subcellular site of expanded Cav2.1 toxicity is controversial and it remains elusive whether SCA6 shares pathogenic cascades with other SCAs. To gain insight into these problems, we studied the cerebellar gene expression patterns of young Sca6 MPI 118Q/118Q knockin (KI) mice, which express mutant Cav2.1 from endogenous locus and faithfully models human SCA6. Comparison of transcriptional changes with those of Sca1 154Q/2Q mice, a faithful KI mouse model of SCA1, revealed that transcriptional signatures in the MPI 118Q/118Q were distinct from those of Sca1 154Q/2Q. Examination of temporal profiles of candidate genes showed that upregulation of those associated with microglial activation was initiated before PC degeneration was apparent and augmented as the disease progressed. Histological analysis of the MPI 118Q/118Q cerebellum confirmed the presence of Iba-1 positive activated microglia. Moreover, predominance of M1-like pro-inflammatory microglia was observed and was concomitant with the increased expression of pro-inflammatory cytokines. These results suggest that the unique transcriptional response, which highlights upregulation of neuroinflammatory genes possibly associated with lysosomal involvement, may play a pivotal role in the pathogenesis. Modulation of innate immune system could pave the way for slowing the progression of SCA6.
Publication Title
Loss of MyD88 alters neuroinflammatory response and attenuates early Purkinje cell loss in a spinocerebellar ataxia type 6 mouse model.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We used microarrays to detail the global gene expression changes during aging in fly heads and identified genes related to the unfolded protein response are up-regulated upon aging.
Publication Title
EDEM Function in ERAD Protects against Chronic ER Proteinopathy and Age-Related Physiological Decline in Drosophila.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In our experiments with a xenograft model, mouse-IFN (mIFN) treatment was suggested to exaggerate the antitumor effects of sorafenib on hepatocellular carcinoma in vivo.
Publication Title
The in vivo antitumor effects of type I-interferon against hepatocellular carcinoma: the suppression of tumor cell growth and angiogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
For the clinical treatment of chronic obstructive pulmonary disease (COPD), it is important not only to improve the airflow limitation by bronchodilation but also to suppress emphysema by controlling inflammation. In this study, we have screened for compounds that prevent elastase-induced airspace enlargement in mice from medicines already used clinically. Mepenzolate bromide, a muscarinic antagonist used to treat gastrointestinal disorders was selected. Intratracheal administration or inhalation of mepenzolate bromide decreased the severity of elastase-induced airspace enlargement, alteration of lung mechanics and respiratory dysfunction. While mepenzolate bromide showed bronchodilatory activity, most of other muscarinic antagonists tested did not improve the elastase-induced pulmonary disorders. Mepenzolate bromide suppressed elastase-induced pulmonary inflammatory responses and production of superoxide anions, and reduced the level of cigarette smoke-induced airspace enlargement and alteration of lung mechanics. Based on these results, we propose that this drug is therapeutically effective for COPD as a consequence of both its anti-inflammatory and bronchodilatory activities.
Publication Title
Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease.
Sample Metadata Fields
Treatment, Time
View Samples- Homo sapiens
- 32 Downloadable Samples
Illumina HiSeq 2000
Description
IPF (n=20) and control (n=19) samples were obtained through the LTRC and were sequenced on an Illumina HiSeq 2000 following TruSeq RNA Sample Prep Kit v2 library preparation. Overall design: Cross-sectional samples were analyzed. IPF diagnosis was based on American Thoracic Society and European Respiratory Society criteria, and all IPF samples displayed typical patterns of usual interstitial pneumonia. RNA libraries were prepared from 200 ng of high quality total RNA according to the manufacturer’s instructions for the TruSeq RNA Sample Prep Kit v2 (Illumina, San Diego, CA). The concentration and size distribution of TruSeq libraries was determined on an Agilent Bioanalyzer DNA 1000 chip (Santa Clara, CA), and a final quantification, using Qubit fluorometry (Invitrogen, Carlsbad, CA), was conducted to confirm sample concentration. Libraries were loaded onto paired end flow cells at concentrations of 8-10 pM to generate cluster densities of 700,000/mm2 following Illumina’s standard protocol using the Illumina cBot and cBot Paired end cluster kit version 3. The flow cells were sequenced as 51 X 2 paired end reads on an Illumina HiSeq 2000 using TruSeq SBS sequencing kit version 3 and SCS version 1.4.8 data collection software. Base-calling was performed using Illumina’s RTA version 1.12.4.2.
Publication Title
Cellular senescence mediates fibrotic pulmonary disease.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples