Biomarkers for Down Syndrome screening in murine fetal liver and placenta
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE24272 | GEO | 2011/05/11
SECONDARY ACCESSION(S): PRJNA133009
REPOSITORIES: GEO
Similar Datasets
Project description: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.
2011-05-11 | E-GEOD-24272 | biostudies-arrayexpress
Project description:The Ts1Cje mouse model of Down syndrome (DS) has partial triplication of mouse chromosome 16, of which a large portion is homologous to human chromosome 21. The mouse model shows an impaired neurogenesis at E14.5. We analyzed the effect of Ts1Cje trisomic region on global gene expression in the embryonic brain of Ts1Cje mice at E14.5.
2019-10-18 | GSE121449 | GEO
Project description:The Ts1Cje mouse model of Down syndrome (DS) has partial triplication of mouse chromosome 16, of which a large portion is homologous to human chromosome 21. The mouse model shows an impaired neurogenesis in hippocampus at 3-month-old . We analyzed the effect of Ts1Cje trisomic region on global gene expression in the adult brain of Ts1Cje mice at 3-month-old.
2021-08-01 | GSE160185 | GEO
Project description:Down syndrome (DS), a genetic condition leading to intellectual disability, is characterized by triplication of human chromosome 21. Neuropathological hallmarks of DS include abnormal central nervous system development that manifests during gestation and extends throughout life. As a result, newborns and adults with DS exhibit cognitive and motor deficits and fail to meet typical developmental and lack independent life skills. As of summer 2020, 13 pharmacological interventions have been tested with little evidence of success in improving cognition in humans with DS. Potential reasons for this failure may be related to the fact that these therapeutic interventions were carried out too late, and not during the prenatal and early postnatal critical periods for brain development. To date, no prenatal treatment studies have been reported in pregnant women carrying fetuses with T21. A limited number of prenatal treatment studies using fluoxetine, maternal choline supplementation and the neuroprotective peptides NAP and SAL have been described using the Ts65Dn mouse model of DS. In our previous studies, we integrated gene expression data from nine different cellular and tissue sources in both humans with DS and mouse models to identify common dysregulated signaling pathways and cellular processes. We demonstrated that pathway abnormalities associated with DS were the result of gene-dosage specific effects and the consequence of a global stress response with activation of compensatory mechanisms. To counteract these genome-wide abnormalities, we used the Connectivity Map database (www.broadinstitute.org/CMap) to discover molecules that could be repurposed to rescue the transcriptome and promote more typical brain development in individuals with DS. One of the molecules that had the most consistent negative scores (hence, negating the dysregulated gene expression signatures in DS) across tissues and species was apigenin (4’, 5, 7-trihydroxyflavone). Here, we hypothesized that prenatal treatment with apigenin would partly rescue the global gene expression dysregulation to improve neurogenesis and postnatal cognitive outcomes in DS. In the current study, we used a human in vitro cell model (amniocytes derived from live fetuses with Trisomy 21 and euploid fetuses) and the Ts1Cje mouse model of DS to evaluate the effects of apigenin as a potential therpay for prenatal brain defects and postnatal cognitive outcome in DS. We demonstrated that apigenin is a safe treatment that can rescue oxidative stress and total antioxidant capacity imbalance in human amniocytes from fetuses with T21. It also improved several postnatal behavioral deficits in the Ts1Cje mouse model. We also showed that apigenin achieves its therapeutic action by triggering the expression of neurogenic genes, suppressing inflammation via inhibiting NFκB and by reducing the production of pro-inflammatory cytokines, while promoting the production of anti-inflammatory cytokines, angiogenic and neurotrophic factors.
2020-09-23 | GSE158377 | GEO
Project description:Down syndrome (DS), a genetic condition leading to intellectual disability, is characterized by triplication of human chromosome 21. Neuropathological hallmarks of DS include abnormal central nervous system development that manifests during gestation and extends throughout life. As a result, newborns and adults with DS exhibit cognitive and motor deficits and fail to meet typical developmental and lack independent life skills. In the last two decades, a number of preclinical treatment studies showed beneficial effects in the Ts65Dn mouse model. As of summer 2020, 13 pharmacological interventions have been tested with little evidence of success in humans with DS. Potential reasons for this failure may be related to the fact that these therapeutic interventions were carried out too late, and not during the prenatal and early postnatal critical periods for brain development. To date, no prenatal treatment studies have been reported in pregnant women carrying fetuses with T21. A limited number of prenatal treatment studies using fluoxetine, maternal choline supplementation and the neuroprotective peptides NAP and SAL have been described using the Ts65Dn mouse model of DS. In our previous studies, we integrated gene expression data from nine different cellular and tissue sources in both humans with DS and mouse models to identify common dysregulated signaling pathways and cellular processes. We demonstrated that pathway abnormalities associated with DS were the result of gene-dosage specific effects and the consequence of a global stress response with activation of compensatory mechanisms. To counteract these genome-wide abnormalities, we used the Connectivity Map database (www.broadinstitute.org/CMap) to discover molecules that could be repurposed to rescue the transcriptome and promote more typical brain development in individuals with DS. One of the molecules that had the most consistent negative scores (hence, negating the dysregulated gene expression signatures in DS) across tissues and species was apigenin (4’, 5, 7-trihydroxyflavone). Here, we hypothesized that prenatal treatment with apigenin would partly rescue the global gene expression dysregulation to improve neurogenesis and postnatal cognitive outcomes in DS. In the current study, we used a human in vitro cell model (amniocytes derived from live fetuses with Trisomy 21 and euploid fetuses) and the Ts1Cje mouse model of DS to evaluate the effects of apigenin as a potential therpay for prenatal brain defects and postnatal cognitive outcome in DS. We demonstrated that apigenin is a safe treatment that can rescue oxidative stress and total antioxidant capacity imbalance in human amniocytes from fetuses with T21. It also improved several postnatal behavioral deficits in the Ts1Cje mouse model. We also showed that apigenin achieves its therapeutic action by triggering the expression of neurogenic genes, suppressing inflammation via inhibiting NFκB and by reducing the production of pro-inflammatory cytokines, while promoting the production of anti-inflammatory cytokines, angiogenic and neurotrophic factors.
2020-09-23 | GSE158376 | GEO
Project description:The Ts1Cje mouse model of Down syndrome (DS) has partial triplication of mouse chromosome 16 (MMU16), which is partially homologous to human chromosome 21. The mouse model develops various neuropathological features identified in DS individuals. We analysed the effect of partial triplication of the MMU16 segment on global gene expression in the cerebral cortex, cerebellum and hippocampus of Ts1Cje mice at 4 time-points; postnatal day (P)1, P15, P30 and P84.
2014-07-23 | GSE49050 | GEO
Project description:The Ts1Cje mouse model of Down syndrome (DS) has partial triplication of mouse chromosome 16 (MMU16), which is partially homologous to human chromosome 21. The mouse model develops various neuropathological features identified in DS individuals. We analysed the effect of partial triplication of the MMU16 segment on global gene expression in the cerebral cortex, cerebellum and hippocampus of Ts1Cje mice at 4 time-points; postnatal day (P)1, P15, P30 and P84. RNA was extracted from thre brain regions (Cerebral cortex, hippocampus and cerebellum) for hybridization to arrays from 3 pairs of Ts1Cje and disomic C57BL/6 littermate control for each timepoints at postnatal (P) day 1, P15, P30 and P84.
2014-07-23 | E-GEOD-49050 | biostudies-arrayexpress
Project description:Down syndrome (DS) is caused by trisomy of chromosome 21 and it predisposes to hematological disorders such as transient myeloproliferative disorder and acute megakaryocytic leukemia. Our previous study identified a gain-of-function mutation of TRIB1 encoding a pseudokinase that suppresses C/EBP and enhances MEK/ERK signaling. In this study, we aimed to examine whether Trib1 expression cooperates with trisomy 21 in the development of leukemia. The wild type or R107L mutant Trib1 was retrovirally introduced into bone marrow cells derived from the Ts1Cje Down syndrome model mice or C57Bl6/J mice. Trib1 expression in hematopoietic cells of Ts1Cje mice accelerated the onset of AML development compared with that in wild type mice. Gene expression analysis showed up-regulation of Hox downstream genes and down-regulation of genes for the myeloid differentiation program and C/EBP targets. These results suggest that Trib1-mediated signaling plays an important role in promoting leukemogenesis in Down syndrome. We used microarrays to detail the global program of gene expression in mouse AML
2022-03-29 | GSE168531 | GEO
Project description:Down syndrome (DS), with trisomy of chromosome 21 (HSA21), is the commonest human aneuploidy. Pre-leukemic myeloproliferative changes in DS fetal livers precedes the acquisition of GATA1 mutations, transient myeloproliferative disorder (DS-TMD) and acute megakaryocytic leukemia (DS-AMKL). Trisomy of the Erg gene is required for myeloproliferation in the Ts(1716)65Dn DS mouse model. We demonstrate here that genetic changes due trisomy of Erg lead to lineage priming of primitive and early multipotential progenitor cells in Ts(1716)65Dn mice, excess megakaryocyte-erythroid progenitors, and malignant myeloproliferation. Correlation of gene expression changes caused by Erg trisomy in Ts(1716)65Dn multilineage progenitor cells with those associated with trisomy 21 in human DS HSCs support a role for ERG as a regulator of hematopoietic lineage potential, trisomy of which drives pre-leukemic changes in DS fetal livers that predispose to subsequent DS-TMD and DS-AMKL.
2015-04-15 | E-MTAB-2574 | biostudies-arrayexpress
Project description:Down Syndrome (DS) results from the trisomy of human chromosome 21 (HSA21). It is still the most frequent intellectual disability, affecting 1 newborn per 700 births. Among candidate genes explaining intellectual disabilities seen in DS patients, the dual specificity tyrosine-phosphorylation regulated kinase 1A, DYRK1A, is located in the DS critical region of chromosome 21. DYRK1A has become a major screening target for the development of selective and potent pharmacological inhibitors. We here investigated the effects of a relatively selective DYRK1A inhibitor, Leucettine 41 (hereafter L41) in three different trisomic mouse models with increasing genetic complexity, Tg(Dyrk1a), Ts65Dn and Dp1Yey. Leucettines are derived from the marine sponge alkaloid Leucettamine B.
2018-10-17 | PXD008419 | Pride