Gene Expression Profiling in a Mouse Model Identifies Fetal Liver- and Placenta-Derived Potential Biomarkers for Down Syndrome Screening

Jeroen L A Pennings,Wendy Rodenburg,Timo M Breit,Maria P H Koster,Peter C J I Schielen,Conny T M Van Oostrom,Sandra Imholz,Annemieke De Vries,Gisela Nogales-Gadea

doi:10.1371/journal.pone.0018866

Jeroen L A Pennings, Wendy Rodenburg + Show 7 more

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https://doi.org/10.1371/journal.pone.0018866

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Abstract

BackgroundAs 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.Methodology/Principal FindingsPlacenta and fetal liver at 15.5 days gestation were analyzed by microarray profiling. We confirmed increased expression of genes located at the trisomic chromosomal region. Overall, between the two genotypes more differentially expressed genes were found in fetal liver than in placenta. Furthermore, the fetal liver data are in line with the hematological aberrations found in humans with Down Syndrome as well as Ts1Cje mice. Together, we found 25 targets that are predicted (by Gene Ontology, UniProt, or the Human Plasma Proteome project) to be detectable in human serum.Conclusions/SignificanceFetal liver might harbor more promising targets for Down Syndrome screening studies. We expect these new targets will help focus further experimental studies on identifying and validating human maternal serum biomarkers for Down Syndrome screening.

Highlights

Prenatal screening for Down Syndrome (DS) has been routinely available for two decades
Genotype confirmation To validate the use of a mouse model for DS in a transcriptomics study, we first compared the expression ratio between Ts1Cje and WT embryos for genes located on chromosome Mmu16
For DS, several mouse models have been developed to study the effect of trisomy in single or multiple genes on DS phenotype and development

Summary

Introduction

Prenatal screening for Down Syndrome (DS) has been routinely available for two decades. Many countries including the Netherlands, have replaced this by the first trimester combined test, which is based on fb-hCG and pregnancy-associated plasma protein A (PAPP-A) serum concentrations, ultrasound nuchal translucency (NT) measurements and maternal age [3]. This latter test has a Detection Rate (DR) of 75–85% at a 5% false positive rate (FPR) [4,5,6]. Since current Down Syndrome screening markers are derived from placenta and fetal liver, these tissues were chosen as target

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Conclusion