Document Detail


Fetal alcohol syndrome (FAS) in C57BL/6 mice detected through proteomics screening of the amniotic fluid.
MedLine Citation:
PMID:  18240165     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Fetal Alcohol Syndrome (FAS), a severe consequence of the Fetal Alcohol Spectrum Disorders, is associated with craniofacial defects, mental retardation, and stunted growth. Previous studies in C57BL/6J and C57BL/6N mice provide evidence that alcohol-induced pathogenesis follows early changes in gene expression within specific molecular pathways in the embryonic headfold. Whereas the former (B6J) pregnancies carry a high-risk for dysmorphogenesis following maternal exposure to 2.9 g/kg alcohol (two injections spaced 4.0 h apart on gestation day 8), the latter (B6N) pregnancies carry a low-risk for malformations. The present study used this murine model to screen amniotic fluid for biomarkers that could potentially discriminate between FAS-positive and FAS-negative pregnancies.
METHODS: B6J and B6N litters were treated with alcohol (exposed) or saline (control) on day 8 of gestation. Amniotic fluid aspirated on day 17 (n = 6 replicate litters per group) was subjected to trypsin digestion for analysis by matrix-assisted laser desorption-time of flight mass spectrometry with the aid of denoising algorithms, statistical testing, and classification methods.
RESULTS: We identified several peaks in the proteomics screen that were reduced consistently and specifically in exposed B6J litters. Preliminary characterization by liquid chromatography tandem mass spectrometry and multidimensional protein identification mapped the reduced peaks to alpha fetoprotein (AFP). The predictive strength of AFP deficiency as a biomarker for FAS-positive litters was confirmed by area under the receiver operating characteristic curve.
CONCLUSIONS: : These findings in genetically susceptible mice support clinical observations in maternal serum that implicate a decrease in AFP levels following prenatal alcohol damage.
Authors:
Susmita Datta; Delano Turner; Reetu Singh; L Bruno Ruest; William M Pierce; Thomas B Knudsen
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Publication Detail:
Type:  Comparative Study; Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Birth defects research. Part A, Clinical and molecular teratology     Volume:  82     ISSN:  1542-0760     ISO Abbreviation:  Birth Defects Res. Part A Clin. Mol. Teratol.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-28     Completed Date:  2008-07-02     Revised Date:  2011-05-05    
Medline Journal Info:
Nlm Unique ID:  101155107     Medline TA:  Birth Defects Res A Clin Mol Teratol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  177-86     Citation Subset:  IM    
Copyright Information:
(c) 2008 Wiley-Liss, Inc.
Affiliation:
Department of Bioinformatics and Biostatistics, School of Public Health and Information Science, University of Louisville, Louisville, Kentucky 40292, USA. susmita.datta@louisville.edu
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MeSH Terms
Descriptor/Qualifier:
Amniotic Fluid / chemistry*
Animals
Biological Markers / analysis
Congenital Abnormalities / etiology
Ethanol
Female
Fetal Alcohol Syndrome / diagnosis*,  pathology
Fetal Resorption / etiology
Fetal Weight / drug effects
Litter Size
Maternal Exposure / adverse effects
Mice
Mice, Inbred C57BL
Pregnancy
Prenatal Diagnosis / methods*
Proteomics*
Sensitivity and Specificity
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
alpha-Fetoproteins / analysis*
Grant Support
ID/Acronym/Agency:
P20-RR/DE17702/DE/NIDCR NIH HHS; P30ES014443-01A1/ES/NIEHS NIH HHS; R01-AA13205/AA/NIAAA NIH HHS; R56 AA013205-05/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/alpha-Fetoproteins; 64-17-5/Ethanol
Comments/Corrections

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