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Strain-dependent effects of alcohol on early mouse embryos


ABSTRACT: EXPERIMENT: Microarray expression profiles derived from the cranial neural folds (headfold) of neurulation-stage mouse embryos 3.0h after maternal alcohol exposure on 8 d.p.c. ANIMAL MODEL: Pregnancies from 2 substrains of C57BL/6 mice that differ in relative risk of Fetal Alcohol Syndrome (FAS): C57BL/6J (B6J) high-risk condition, and C57BL/6NCrl (B6N) low-risk condition. EXPOSURE: Dams dosed with ethanol (EtOH) by intraperitoneal injection at 2.9 g EtOH per kg body weight. Controls received vehicle (saline) alone. A third group of dams received EtOH + 4.0 mg/kg PK11195, a specific high-affinity ligand to the 18 KDa mitochondrial peripheral benzodiazepine receptor site. INTERVAL: High blood alcohol content must be sustained in dams for several hours to invoke FAS and is traditionally accomplished by a double injection of EtOH 4.0h apart. Since these embryos were harvested for genetic analysis 1h before dams would have gotten the second alcohol injection, the interval represents a snapshot of the critical response, prior to the second maternal injection that invokes greater risk. Counter-exposure to PK11195 significantly lowers the adverse response of B6J embryos to EtOH. PLATFORM: Two independent assays run. The first dataset (PE), run April 2002 – January 2003, used samples pooled from 2 litters (PE) and the platform was a two-channel MPS621 array (http://www.lifesciences.perkinelmer.com/). This platform has 4800 sequence-verified gene elements derived from over 50 different human cDNA libraries reflecting a variety of well-annotated cellular processes and disease pathways. The second dataset (AF), run between May 2005 – November 2005, used samples pooled from 1 litter and the platform was Affymetrix GeneChip® Mouse Genome 430A 2.0 Array (http://www.affymetrix.com/). The MG430A 2.0 platform has 45,102 oligonucleotide probe cells representing approximately 14,000 well-characterized genes in the draft mouse genome assembly. The corresponding GEO samples are GSM12218 - GSM12227 for the two-channel PE arrays, and GSM136067 - GSM136078 for the one-channel AF arrays. Keywords = fetal alcohol syndrome Keywords = alcohol-related birth defects Keywords = EtOH Keywords = PK11195 Keywords = embryo Keywords = strain differences Keywords: Ordered Assay of early mouse embryos during pathogenesis of Fetal Alcohol Syndrome (FAS). Replicate RNA samples were arrayed by one-channel oligonucleotide (Affymetrix) or two-channel cDNA (Perkin-Elmer) platforms.

ORGANISM(S): Mus musculus

SUBMITTER: Maia Green 

PROVIDER: E-GEOD-1074 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Reprogramming of genetic networks during initiation of the Fetal Alcohol Syndrome.

Green Maia L ML   Singh Amar V AV   Zhang Yihzi Y   Nemeth Kimberly A KA   Sulik Kathleen K KK   Knudsen Thomas B TB  

Developmental dynamics : an official publication of the American Association of Anatomists 20070201 2


Fetal Alcohol Spectrum Disorders (FASD) are birth defects that result from maternal alcohol use. We used a non a priori approach to prioritize candidate pathways during alcohol-induced teratogenicity in early mouse embryos. Two C57BL/6 substrains (B6J, B6N) served as the basis for study. Dosing pregnant dams with alcohol (2x 2.9 g/kg ethanol spaced 4 hr on day 8) induced FASD in B6J at a higher incidence than B6N embryos. Counter-exposure to PK11195 (4 mg/kg) significantly protected B6J embryos  ...[more]

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