UseCases_ArguminSci_Discourse  

PubMed:18412970 JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
T1 0-129 DRI_Background denotes Elucidating a normal function of huntingtin by functional and microarray analysis of huntingtin-null mouse embryonic fibroblasts.
T2 142-238 DRI_Challenge denotes The polyglutamine expansion in huntingtin (Htt) protein is a cause of Huntington's disease (HD).
T3 239-340 DRI_Background denotes Htt is an essential gene as deletion of the mouse Htt gene homolog (Hdh) is embryonic lethal in mice.
T4 341-540 DRI_Outcome denotes Therefore, in addition to elucidating the mechanisms responsible for polyQ-mediated pathology, it is also important to understand the normal function of Htt protein for both basic biology and for HD.
T5 550-834 DRI_Approach denotes To systematically search for a mouse Htt function, we took advantage of the Hdh +/- and Hdh-floxed mice and generated four mouse embryonic fibroblast (MEF) cells lines which contain a single copy of the Hdh gene (Hdh-HET) and four MEF lines in which the Hdh gene was deleted (Hdh-KO).
T6 835-950 DRI_Background denotes The function of Htt in calcium (Ca2+) signaling was analyzed in Ca2+ imaging experiments with generated cell lines.
T7 951-1183 DRI_Outcome denotes We found that the cytoplasmic Ca2+ spikes resulting from the activation of inositol 1,4,5-trisphosphate receptor (InsP3R) and the ensuing mitochondrial Ca2+ signals were suppressed in the Hdh-KO cells when compared to Hdh-HET cells.
T8 1184-1349 DRI_Approach denotes Furthermore, in experiments with permeabilized cells we found that the InsP3-sensitivity of Ca2+ mobilization from endoplasmic reticulum was reduced in Hdh-KO cells.
T9 1350-1420 DRI_Background denotes These results indicated that Htt plays an important role in modulating
T10 1421-1441 Token_Label.OUTSIDE denotes InsP3R-mediated Ca2+
T11 1442-1452 DRI_Background denotes signaling.
T12 1453-1591 DRI_Approach denotes To further evaluate function of Htt, we performed genome-wide transcription profiling of generated Hdh-HET and Hdh-KO cells by microarray.
T13 1592-1819 DRI_Outcome denotes Our results revealed that 106 unique transcripts were downregulated by more than two-fold with p < 0.05 and 173 unique transcripts were upregulated at least two-fold with p < 0.05 in Hdh-KO cells when compared to Hdh-HET cells.
T14 1820-1925 DRI_Background denotes The microarray results were confirmed by quantitative real-time PCR for a number of affected transcripts.
T15 1926-2041 DRI_Background denotes Several signaling pathways affected by Hdh gene deletion were identified from annotation of the microarray results.
T16 2054-2204 DRI_Background denotes Functional analysis of generated Htt-null MEF cells revealed that Htt plays a direct role in Ca2+ signaling by modulating InsP3R sensitivity to InsP3.
T17 2205-2407 DRI_Outcome denotes The genome-wide transcriptional profiling of Htt-null cells yielded novel and unique information about the normal function of Htt in cells, which may contribute to our understanding and treatment of HD.