PMID- 10419687
OWN - NLM
STAT- MEDLINE
DCOM- 19990824
LR  - 20161124
IS  - 0012-1606 (Print)
IS  - 0012-1606 (Linking)
VI  - 212
IP  - 1
DP  - 1999 Aug 1
TI  - Neurofibromin deficiency in mice causes exencephaly and is a modifier for Splotch
      neural tube defects.
PG  - 80-92
AB  - 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.
CI  - Copyright 1999 Academic Press.
FAU - Lakkis, M M
AU  - Lakkis MM
AD  - Department of Medicine, University of Pennsylvania School of Medicine,
      Philadelphia, Pennsylvania, 19104, USA.
FAU - Golden, J A
AU  - Golden JA
FAU - O'Shea, K S
AU  - O'Shea KS
FAU - Epstein, J A
AU  - Epstein JA
LA  - eng
GR  - HD03267/HD/NICHD NIH HHS/United States
GR  - HD26979/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Dev Biol
JT  - Developmental biology
JID - 0372762
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Neurofibromin 1)
RN  - 0 (PAX3 Transcription Factor)
RN  - 0 (PAX3 protein, human)
RN  - 0 (Paired Box Transcription Factors)
RN  - 0 (Proteins)
RN  - 0 (Transcription Factors)
RN  - 138016-91-8 (Pax3 protein, mouse)
SB  - IM
MH  - Animals
MH  - Brain/*abnormalities/metabolism
MH  - DNA-Binding Proteins/*genetics
MH  - Female
MH  - Ganglia, Spinal/abnormalities
MH  - Genotype
MH  - In Situ Hybridization
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neural Tube Defects/*genetics
MH  - Neurofibromin 1
MH  - PAX3 Transcription Factor
MH  - Paired Box Transcription Factors
MH  - Phenotype
MH  - Proteins/genetics/*physiology
MH  - Time Factors
MH  - *Transcription Factors
EDAT- 1999/07/27 00:00
MHDA- 1999/07/27 00:01
CRDT- 1999/07/27 00:00
PHST- 1999/07/27 00:00 [pubmed]
PHST- 1999/07/27 00:01 [medline]
PHST- 1999/07/27 00:00 [entrez]
AID - 10.1006/dbio.1999.9327 [doi]
AID - S0012-1606(99)99327-2 [pii]
PST - ppublish
SO  - Dev Biol. 1999 Aug 1;212(1):80-92. doi: 10.1006/dbio.1999.9327.