Arsenic-induced gene expression changes in the neural tube of folate transport defective mouse embryos.

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Wlodarczyk BJ, Cabrera RM, Hill DS, Bozinov D, Zhu H, Finnell RH

Arsenic-induced gene expression changes in the neural tube of folate transport defective mouse embryos.

Neurotoxicology. 2006 Jul;27(4):547-57. Epub 2006 Apr 18.

PubMed ID

16620997 [ View in PubMed

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Abstract

Arsenic injected intraperitoneally (i.p.) during early organogenesis to small pregnant laboratory rodents (mouse, rat, and hamster) induces several congenital defects in the progeny. Among those abnormalities consistently and predominantly observed are exencephaly and encephalocele. These severe defects of the central nervous system originate from a corrupted process of neurulation and are better known as neural tube defects (NTDs). In order to understand the mechanism of arsenate-induced NTDs, we designed studies in which highly sensitive Folr2 nullizygous mice were injected intraperitoneally with sodium arsenate at the beginning of the neural tube formation process. This specific knockout mouse and the arsenic exposure conditions were chosen as they were known to provide a high incidence of exencephaly in exposed embryos. We have applied gene expression technology to the anterior neural tube. This allowed us to study arsenic-induced changes in patterns of gene expression that may contribute to the development of neural tube defects in these mice. Using extensive data analysis approaches including hierarchical clustering and gene ontology analysis, we identified several candidate genes as well as important ontology groups that may be responsible for arsenic's teratogenicity. Changes in the expression of several genes in response to arsenic treatment in our model had previously been demonstrated by other investigators to also induce NTDs in murine model systems. These include: engrailed 1 (En-1), platelet derived growth factor receptor alpha (Pdgfralpha) and ephrinA7 (EphA7). We also found several gene ontology groups that could be implicated in arsenic's underlying teratogenicity: morphogenesis, oxidative phosporylation, redox response, and regulation of I-kappaB kinase/NF-kappaB cascade. Additionally, we revealed new target genes which may be responsible for arsenic disrupted oxidative phosphorylation.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Folic acid	Folate receptor beta	Protein	Humans	Unknown	Binder	Details