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Early transcription...
Early transcriptional responses in mouse embryos as a basis for selection of molecular markers predictive of valproic acid teratogenicity
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- Kultima, Kim (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Centrum för bioinformatik
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- Jergil, Måns (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Salter, Hugh (författare)
- Uppsala universitet,Centrum för bioinformatik
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Gustafson, Anne-Lee (författare)
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- Dencker, Lennart (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Stigson, Michael (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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(creator_code:org_t)
- Elsevier BV, 2010
- 2010
- Engelska.
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 30:3, s. 457-468
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Cell-based in vitro assays would potentially reduce animal testing in preclinical drug development. Mouse embryos exposed to the teratogenic drug valproic acid (VPA) in utero for 1.5, 3 or 6h on gestational day 8 were analyzed using microarrays. Significant effects on gene expression were observed already at 1.5h, and 85 probes were deregulated across all time points. To find transcriptional markers of VPA-induced developmental toxicity, the in vivo data were compared to previous in vitro data on embryonal carcinoma P19 cells exposed to VPA for 1.5, 6 or 24h. Maximal concordance between embryos and cells was at the 6-h time points, with 163 genes showing similar deregulation. Developmentally important Gene Ontology terms, such as "organ morphogenesis" and "tube development" were overrepresented among putative VPA target genes. The genes Gja1, Hap1, Sall2, H1f0,Cyp26a1, Fgf15, Otx2, and Lin7b emerged as candidate in vitro markers of potential VPA-induced teratogenicity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Nyckelord
- Gene Ontology
- In vitro toxicology
- Microarray
- Mouse embryo
- Neural tube defects
- Teratogen
- Toxicogenomics
- Valproic acid
- PHARMACY
- FARMACI
- Biology
- Biologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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