Linked Life Data

10419687

Source:http://linkedlifedata.com/resource/pubmed/id/10419687

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-8-24
pubmed:abstractText
Neural tube defects are common and serious human congenital anomalies. These malformations have a multifactorial etiology and can be reproduced in mouse models by mutations of numerous individual genes and by perturbation of multiple environmental factors. The identification of specific genetic interactions affecting neural tube closure will facilitate our understanding of molecular pathways regulating normal neural development and will enhance our ability to predict and modify the incidence of spina bifida and other neural tube defects. Here, we report a genetic interaction between Nf1, encoding the intracellular signal transduction protein neurofibromin, and Pax3, a transcription factor gene mutated in the Splotch mouse. Both Pax3 and Nf1 are important for the development of neural crest-derived structures and the central nervous system. Splotch is an established model of folate-sensitive neural tube defects, and homozygous mutant embryos develop spina bifida and sometimes exencephaly. Neural development is grossly normal in heterozygotes and neural tube defects are not seen. In contrast, we found a low incidence of neural tube defects in heterozygous Splotch mice that also harbored a mutation in one Nf1 allele. All compound homozygotes had severe neural tube defects and died earlier in embryogenesis than either Nf1(-/-) or Sp(-/-) embryos. We also report occasional exencephaly in Nf1(-/-) mice and identify more subtle CNS abnormalities in normal-appearing Nf1(-/-) embryos. Though other genetic loci and environmental factors affect the incidence of neural tube defects in Splotch mice, these results establish Nf1 as the first known gene to act as a modifier of neural tube defects in Splotch.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0012-1606
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
212
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
80-92
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Neurofibromin deficiency in mice causes exencephaly and is a modifier for Splotch neural tube defects.
pubmed:affiliation
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.