Mouse models of neural tube defects: Investigating preventive mechanisms

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 know...

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Published in:American journal of medical genetics. Part C, Seminars in medical genetics Seminars in medical genetics, 2005-05, Vol.135C (1), p.31-41
Main Authors: Greene, Nicholas D.E., Copp, Andrew J.
Format: Article
Language:English
Subjects:
Animals
curly tail
Disease Models, Animal
Embryonic Development - genetics
folic acid
Humans
inositol
Mice
Mice, Knockout
mouse model
neural tube defects
Neural Tube Defects - embryology
Neural Tube Defects - etiology
Neural Tube Defects - prevention & control
teratogen
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Summary: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.
ISSN:1552-4868
1552-4876
DOI:10.1002/ajmg.c.30051