Proteome analysis of huntingtin knock-in allelic series - Heart
Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ Orbitrap Velos
ORGANISM(S): Mus Musculus (mouse)
DISEASE(S): Huntington Disease
SUBMITTER: 
Christoph Schaab
LAB HEAD: Christoph Schaab
PROVIDER: PXD010958 | Pride | 2018-09-03
REPOSITORIES: Pride
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Project description:The objective of this project is to study the proteome in different tissues of huntingtin knock-in allelic series in mice. In the current part of the study, liver samples from the complete remaining allelic series collected at 2, 6, and 10 months were analyzed. To this end, comprehensive quantitative, label-free proteome analysis was performed using Evotec’s quantitative Deep Proteome Profiling technology.
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Project description:Animal models play a critical role in the study of Huntington’s disease (HD), for example to elucidate underlying molecular mechanisms or to develop novel therapeutic venues. One of the first transgenic mouse models of HD, the R6/2 line, has been described in 1996 and has since become one of the most studied models of the disease (Mangiarini et al. 1996; Li, Popovic & Brundin 2005). R6/2 mice express the human exon 1 under control of the human huntingtin promoter at around 75% of the endogenous levels. The expression of the exon 1 with a CAG repeat length of around 115 evokes rapid disease progression and animals display multiple HD-associated neuropathological changes. First signs of disease can occur as early as three weeks and mice are severely impaired by the age of 8-12 weeks. The expected life span is 13-16 weeks (Li, Popovic & Brundin 2005). Here we were interested in the changes occurring in the proteomic landscape as well as in phosphoproteomic signaling networks in the R6/2 mouse model as compared to wild type mice. To this end, we performed comprehensive quantitative phosphoproteome and proteome analyses of striatum of one, two, and three months old mice of both genotypes. A total of nine or more samples per group was analyzed according to the experimental layout shown above. To allow for accurate quantification, peptides of each sample were labelled using tandem mass tags (TMT) and replicates of different conditions were combined. Each combined sample contained an aliquot of a pooled sample consisting of 12 sample lysates. This pooled sample was intended to serve as a reference to allow for quantitative comparison between all combined samples.
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Project description:Background: To understand gene expression networks leading to functional properties of the soybean seed, we have undertaken a detailed examination of soybean seed development during the stages of major accumulation of oils, proteins, and starches, as well as the desiccating and mature stages, using microarrays consisting of up to 27,000 soybean cDNAs. Results: It was discovered that genes related to cell growth and maintenance processes, as well as energy processes like photosynthesis, decreased in expression levels as the cotyledons approached the mature, dry stage. Genes involved with some storage proteins had their highest expression levels at the stage of largest fresh weight. However, genes encoding many transcription factors and DNA binding proteins showed higher expression levels in the desiccating and dry seeds than in most of the green stages. Conclusions: Data on 27,000 cDNAs have been obtained over five stages of soybean development, including the stages of major accumulation of agronomically-important products, using microarrays. Of particular interest are the genes found to peak in expression at the desiccating and dry seed stages, such as those annotated as transcription factors, which may indicate the preparation of pathways that will be needed later in the early stages of imbibition and germination. Five stages of development of soybean cotyledons were studied. The first three, with fresh weights of 25-50mg, 75-100mg, and 400-500mg, were green in color. The last two, yellow-colored cotyledons with a fresh weight of 200-300mg and dry whole seeds approximately 100-200mg in weight, were desiccating and yellow/brown in color. The green stage of 100-200mg fresh weight cotyledons was used as a reference for all other stages. Four replicates, including two dye swaps, were made of each of the first three (green) stages. Two replicates, including one dye swap, were made of each of the last two (yellow/dry) stages. The results from three different platforms (GPL229, GPL1012, and GPL1013) were combined.
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