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Using zebrafish to identify and characterize gene‐ethanol interactions (540.10)
Author(s) -
Lovely C.,
McCarthy Neil,
Sidik Alfire,
Swartz Mary,
Eberhart Johann
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.540.10
Subject(s) - zebrafish , phenotype , biology , genetics , mutant , haploinsufficiency , genetic screen , gene , candidate gene , mutation
Fetal Alcohol Spectrum Disorders (FASD) is a complex set of ethanol‐induced defects with diverse phenotypes, particularly to the face. Though little is known of the genetic predisposition to FASD, this predisposition may help explain variation within FASD. The zebrafish is well suited for identifying and characterizing gene‐ethanol interactions because of its external fertilization, transparency, rapid development and genetic amenability. Across a set of small genetic screens, we have identified gene‐ethanol interactions in the Pdgf, Fgf, Bmp, and Wnt signaling pathways. Synergy is an underlying commonality among these interactions. Ethanol‐induced phenotypes are not predicted on the basis of the untreated mutant phenotype, and ethanol‐induced haploinsufficiency is observed that is not present in the untreated heterozygotes. For instance, a cell migratory defect causes facial defects in untreated pdgfra mutants with no elevation in cell death. Ethanol exposure results in a dramatic increase in cell death leading to facial defects in the majority of heterozygotes. The phenotypic spectrum for each gene‐ethanol interaction is unique, supporting the model that susceptibility loci govern some variation in FASD. Because of the success of our initial screens, we initiated a forward genetic screen to identify novel ethanol‐sensitive mutations. We have recovered and are currently characterizing 8 ethanol‐sensitive mutants. Most of these mutants display no overt phenotype in the absence of ethanol and genetic mapping of one of these places it in a region of the genome not containing a previously characterized mutant. These data demonstrate that zebrafish will be a useful model to identify and characterize gene‐ethanol interactions that may lead to variability in FASD. Grant Funding Source : Supported by ABMRF and NIH