Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of cerebellum cells from wild type mice or mice overexpressing TATA-binding protein (TBP) or a mutant version of TBP

ABSTRACT: Transcription profiles were obtained for 2-month old mice. Three lines (WT, TBP-13Q12, and TBP105Q) were used in these experiments.

Wild-type and 13Q mice are normal. The 13Q mice overexpress the normal protein on the RNA but not protein level and do not show a phenotype. The 105Q mice express a mutant version of the protein TBP and faithfully model the disease SCA17 (spinocerebellar ataxia-17, huntington disease-like 4, HDL4).

The constructs containing mixed CAG/CAA trinucleotide repeats (and encoding polyglutamine tracts) of variable length were made using a previously described method (Michalik A et al., Biotechniques, 2001). Briefly, synthetic CAG/CAA oligonucleotides were subcloned into a cDNA construct of the normal mouse (13 CAG/CAA) TBP gene. Because of the mixed nature of the repeat, its length is stable in mitotic and meiotic transmission.

ORGANISM(S): Mus musculus

SUBMITTER: Meyer Friedman

PROVIDER: E-MEXP-1314 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Polyglutamine domain modulates the TBP-TFIIB interaction: implications for its normal function and neurodegeneration.

Friedman Meyer J MJ Shah Anjali G AG Fang Zhi-Hui ZH Ward Elizabeth G EG Warren Stephen T ST Li Shihua S Li Xiao-Jiang XJ

Nature neuroscience 20071111 12

Expansion of the polyglutamine (polyQ) tract in human TATA-box binding protein (TBP) causes the neurodegenerative disease spinocerebellar ataxia 17 (SCA17). It remains unclear how the polyQ tract regulates normal protein function and induces selective neuropathology in SCA17. We generated transgenic mice expressing polyQ-expanded TBP. These mice showed weight loss, progressive neurological symptoms and neurodegeneration before early death. Expanded polyQ tracts reduced TBP dimerization but enhan ...[more]

PMID: 17994014

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Project description:Spinocerebellar ataxia type 3 (SCA3) is one of the polyglutamine (polyQ) diseases, which are caused by a CAG repeat expansion within the coding region of the associated genes. The CAG repeat specifies glutamine, and the expanded polyQ domain with mutation confers dominant toxicity on the protein. Traditionally, studies have focused on protein toxicity in polyQ disease mechanisms. Recent findings, however, demonstrate that the CAG repeat RNA, which encodes the toxic polyQ protein, also contributes to the disease in Drosophila. To provide insight into the nature of the RNA toxicity, we extracted brain-enriched RNA from flies expressing a toxic CAG repeat mRNA (CAG100) and a non-toxic interrupted CAA/G mRNA repeat (CAA/G105) for microarray analysis. This approach identified a set of genes that are differentially expressed specifically in CAG100 flies. Four independent replicates of flies expressing CAG0, CAG100, or CAA/G105 by elav-GAL4 were collected at 3 days. The transgenes are DsRed with either (CAG0) no CAG repeat in the 3'UTR, (CAG100) a CAG repeat of 100 CAGs in the 3'UTR, or (CAA/G105) an interrupted CAA CAG repeat in the 3'UTR (ref: Li et al., Nature 453:1107) The transgenes were adjusted to match in mRNA expression such that CAG0 flies had one copy of the transgene, CAG100 flies had 5 copies, and CAA/G105 had two copies. Fly brain tissue (about 20 brains per sample, dissected from head capsule, eyes, lamina and outer medulla removed) was dissected in cold phosphate buffered saline (PBS) and stored in Trizol reagent (Invitrogen Corporation, Carlsbad, CA) at -80Ë?C. Total brain RNA was extracted and purified using TRIzol reagent (Invitrogen) and the RNeasy Mini system (Qiagen), and treated with RNase-free DNase I (Qiagen). To define genes whose expression is altered in response to a toxic CAG repeat RNA, we compared CAG100 flies with age-matched flies expressing CAG0. To exclude transcriptional changes in response to a non-toxic trinucleotide repeat, a second gene list was generated by comparing CAA/G105 flies with age-matched CAG0 flies.

Dataset Information

Transcription profiling of cerebellum cells from wild type mice or mice overexpressing TATA-binding protein (TBP) or a mutant version of TBP

Publications

Polyglutamine domain modulates the TBP-TFIIB interaction: implications for its normal function and neurodegeneration.

Similar Datasets

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