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Genetic Basis of Susceptibility to Environmentally Induced Neural Tube Defects
Author(s) -
FINNELL RICHARD H.,
GELINEAUVAN WAES JANEE,
BENNETT GREGORY D.,
BARBER ROBERT C.,
WLODARCZYK BOGDAN,
SHAW GARY M.,
LAMMER EDWARD J.,
PIEDRAHITA JORGE A.,
EBERWINE JAMES H.
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb06886.x
Subject(s) - neural tube , folate receptor , biology , gene , neural tube defect , in utero , genetics , transgene , teratology , neuroepithelial cell , genetic predisposition , embryo , methylenetetrahydrofolate reductase , folic acid , receptor , fetus , allele , pregnancy , medicine , embryonic stem cell , cancer , cancer cell
A bstract : 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.