title: Genetic basis of susceptibility to environmentally induced neural tube defects.
abstract: Neural tube defects (NTDs) are among the most common of all human congenital defects, with multifactorial etiologies comprising both environmental and genetic components. Several murine model systems have been developed in an effort to elucidate genetic factors regulating expression of NTDs. Strain-dependent differences in susceptibility to teratogenic insults and altered patterns of gene expression observed within the neuroepithelium of affected embryos support the hypothesis that subtle genetic changes can result in NTDs. Since several affected genes are folate-regulated, transgenic knockout mice lacking a functional folate receptor were developed. Nullizygous embryos died in utero with significant morphological defects, supporting the critical role of folic acid in early embryogenesis. While epidemiological studies have not established an association between polymorphisms in the human folate receptor gene and NTDs, it is known that folate supplementation reduces infant NTD risk. Continued efforts are therefore necessary to reveal the mechanism by which folate works and the nature of the gene(s) responsible for human NTDs.
authors.affiliation: Center for Human Molecular Genetics, University of Nebraska Medical Center, Omaha 68198-5455, USA. rfinnell@unmc.edu
authors.forename: R H
authors.initials: RH
authors.lastname: Finnell
authors.forename: J
authors.initials: J
authors.lastname: Gelineau-van Waes
authors.forename: G D
authors.initials: GD
authors.lastname: Bennett
authors.forename: R C
authors.initials: RC
authors.lastname: Barber
authors.forename: B
authors.initials: B
authors.lastname: Wlodarczyk
authors.forename: G M
authors.initials: GM
authors.lastname: Shaw
authors.forename: E J
authors.initials: EJ
authors.lastname: Lammer
authors.forename: J A
authors.initials: JA
authors.lastname: Piedrahita
authors.forename: J H
authors.initials: JH
authors.lastname: Eberwine
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D016172:DNA Fingerprinting; D004195:Disease Models, Animal; D005314:Embryonic and Fetal Development / Q000235:genetics; D004785:Environmental Pollutants / Q000633:toxicity*; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism / Q000494:pharmacology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005865:Gestational Age; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006979:Hyperthermia, Induced / Q000009:adverse effects; D051379:Mice; D018345:Mice, Knockout; D009436:Neural Tube Defects / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018807:Polymorphism, Single-Stranded Conformational; D011956:Receptors, Cell Surface; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D004785:Environmental Pollutants; D058973:Folate Receptors, GPI-Anchored; D006133:Growth Substances; D011956:Receptors, Cell Surface; D014635:Valproic Acid; D005492:Folic Acid