PUBLICATION
Novel ethanol-sensitive mutants identified in an F3 forward genetic screen
- Authors
- Swartz, M.E., Lovely, C.B., McCarthy, N., Kuka, T., Eberhart, J.K.
- ID
- ZDB-PUB-191120-10
- Date
- 2019
- Source
- Alcoholism, clinical and experimental research 44(1): 56-65 (Journal)
- Registered Authors
- Eberhart, Johann, Lovely, Ben, McCarthy, Neil, Swartz, Mary
- Keywords
- none
- MeSH Terms
-
- Animals
- Craniofacial Abnormalities/chemically induced
- Craniofacial Abnormalities/genetics
- Disease Models, Animal*
- Ethanol/toxicity*
- PubMed
- 31742718 Full text @ Alcoholism Clin. Exp. Res.
Abstract
Background Fetal Alcohol Spectrum Disorders (FASD), collectively refers to all deleterious outcomes due to prenatal alcohol exposures. Alterations to the face are common phenotypes in FASD. While alcohol exposure is the underlying cause of FASD, many variables modify the outcomes of such exposures. Genetic risk is one such variable, yet we still have a limited understanding of the nature of the genetic loci mediating susceptibility to FASD.
Methods We employed ENU-based random mutagenesis in zebrafish to identify mutations that enhanced the teratogenicity of ethanol. F3 embryos obtained from 126 inbred F2 families were exposed to 1% ethanol in the medium (approximately 41 mM tissue levels). Zebrafish stained with Alcian Blue and Alizarin Red were screened for qualitative alterations to the craniofacial skeleton between 4 to 7 days post fertilization (dpf).
Results In all, we recovered six ethanol-sensitive mutants, five from the genetic screen itself and one as a background mutation in one of our wild-type lines. Each mutant has a unique ethanol-induced phenotype relative to the other mutant lines. All but one mutation appears to be recessive in nature and only one mutant, au29, has apparent craniofacial defects in the absence of ethanol. To validate the genetic screen, we genetically mapped au29 and found that it carries a mutation in a previously uncharacterized gene, si:dkey-88l16.3.
Conclusions The phenotypes of these ethanol-sensitive mutants differ from those in previous characterizations of gene-ethanol interactions. Thus, each mutant is likely to provide novel insights into ethanol teratogenesis. Given that most of these mutants only have craniofacial defects in the presence of ethanol and our mapping of au29, it is also likely that many of the mutants will be previously uncharacterized. Collectively, our findings point to the importance of unbiased genetic screens in the identification, and eventual characterization, of risk alleles for FASD.
Genes / Markers
Figure Gallery (9 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping