Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Biomarkers for Down Syndrome screening in murine fetal liver and placenta

ABSTRACT: The Ts1Cje mouse strain (Sago, 1998) contains a segmental trisomy of mouse chromosome 16 orthologous to the region of human chromosome 21 commonly associated with Down Syndrome. In this study, fetuses were obtained from wildtype mothers bred with either wildtype or Ts1Cje males. Gene expression profiles in fetal liver and placenta of wildtype and Ts1Cje fetuses were compared, to identify potential markers for application in human prenatal DS screening. A 48 array study with 24 arrays for placenta and 24 for fetal liver. For each tissue we used RNA from 24 individual embryos, i.e. six male and six female embryos from both genotypes.

ORGANISM(S): Mus musculus

SUBMITTER: Jeroen Pennings

PROVIDER: E-GEOD-24272 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression profiling in a mouse model identifies fetal liver- and placenta-derived potential biomarkers for Down Syndrome screening.

Pennings Jeroen L A JL Rodenburg Wendy W Imholz Sandra S Koster Maria P H MP van Oostrom Conny T M CT Breit Timo M TM Schielen Peter C J I PC de Vries Annemieke A

PloS one 20110414 4

<h4>Background</h4>As a first step to identify novel potential biomarkers for prenatal Down Syndrome screening, we analyzed gene expression in embryos of wild type mice and the Down Syndrome model Ts1Cje. Since current Down Syndrome screening markers are derived from placenta and fetal liver, these tissues were chosen as target.<h4>Methodology/principal findings</h4>Placenta and fetal liver at 15.5 days gestation were analyzed by microarray profiling. We confirmed increased expression of genes l ...[more]

PMID: 21533146

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Project description:Cellular stress responses are frequently presumed to be more sensitive than traditional ecotoxicological life cycle endpoints such as survival and growth. Yet, the focus to reduce test duration and to generate more sensitive endpoints has caused transcriptomics studies to be performed at low doses during short exposures, separately and independently from traditional ecotoxicity tests, making comparisons with life cycle endpoints indirect. Therefore we aimed to directly compare the effects on growth, survival and gene expression of the non-biting midge Chironomus riparius. To this purpose, we analyzed simultaneously life cycle and transcriptomics responses of chironomid larvae exposed to four model toxicants. We observed that already at the lowest test concentrations many transcripts were significantly differentially expressed, while the life cycle endpoints of C. riparius were hardly affected. Analysis of the differentially expressed transcripts showed that at the lowest test concentrations substantial and biologically relevant cellular stress was induced and that many transcripts responded already maximally at these lowest test concentrations. The direct comparison between molecular en life cycle responses after fourteen days of exposure revealed that gene expression is more sensitive to toxicant exposure than life cycle endpoints, underlining the potential of transcriptomics for ecotoxicity testing and environmental risk assessment. Cellular stress responses are frequently presumed to be more sensitive than traditional ecotoxicological life cycle endpoints such as survival and growth. Yet, the focus to reduce test duration and to generate more sensitive endpoints has caused transcriptomics studies to be performed at low doses during short exposures, separately and independently from traditional ecotoxicity tests, making comparisons with life cycle endpoints indirect. Therefore we aimed to directly compare the effects on growth, survival and gene expression of the non-biting midge Chironomus riparius. To this purpose, we analyzed simultaneously life cycle and transcriptomics responses of chironomid larvae exposed to four model toxicants. We observed that already at the lowest test concentrations many transcripts were significantly differentially expressed, while the life cycle endpoints of C. riparius were hardly affected. Analysis of the differentially expressed transcripts showed that at the lowest test concentrations substantial and biologically relevant cellular stress was induced and that many transcripts responded already maximally at these lowest test concentrations. The direct comparison between molecular en life cycle responses after fourteen days of exposure revealed that gene expression is more sensitive to toxicant exposure than life cycle endpoints, underlining the potential of transcriptomics for ecotoxicity testing and environmental risk assessment. Four 14-day Chironomus riparius sediment toxicity tests were conducted, one with each toxicant. The surviving larvae were individually flash frozen in liquid nitrogen. For each toxicant we analyzed the gene expression of larvae exposed to low, intermediate and high concentrations. We also included a control and a solvent control. For each treatment we analyzed 10 replicates (individual larvae).

Dataset Information

Biomarkers for Down Syndrome screening in murine fetal liver and placenta

Publications

Gene expression profiling in a mouse model identifies fetal liver- and placenta-derived potential biomarkers for Down Syndrome screening.

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