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Mouse models of neural tube defects: Investigating preventive mechanisms
Author(s) -
Greene Nicholas D.E.,
Copp Andrew J.
Publication year - 2005
Publication title -
american journal of medical genetics part c: seminars in medical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.419
H-Index - 101
eISSN - 1552-4876
pISSN - 1552-4868
DOI - 10.1002/ajmg.c.30051
Subject(s) - neural tube , anencephaly , spina bifida , folic acid , neural tube defect , medicine , exencephaly , teratology , gene knockout , bioinformatics , pregnancy , biology , genetics , fetus , embryo , surgery , gene
Neural tube defects (NTD), including anencephaly and spina bifida, are a group of severe congenital abnormalities in which the future brain and/or spinal cord fail to close. In mice, NTD may result from genetic mutations or knockouts, or from exposure to teratogenic agents, several of which are known risk factors in humans. Among the many mouse NTD models that have been identified to date, a number have been tested for possible primary prevention of NTD by exogenous agents, such as folic acid. In genetic NTD models such as Cart1 , splotch , Cited2 , and crooked tail , and NTD induced by teratogens including valproic acid and fumonisins, the incidence of defects is reduced by maternal folic acid supplementation. These folate‐responsive models provide an opportunity to investigate the possible mechanisms underlying prevention of NTD by folic acid in humans. In another group of mouse models, that includes curly tail , axial defects , and the Ephrin‐A5 knockout, NTD are not preventable by folic acid, reflecting the situation in humans in which a subset of NTD appear resistant to folic acid therapy. In this group of mutants alternative preventive agents, including inositol and methionine, have been shown to be effective. Overall, the data from mouse models suggests that a broad‐based in utero therapy may offer scope for prevention of a greater proportion of NTD than is currently possible. © 2005 Wiley‐Liss, Inc.