Ethanol is the most common teratogen and the leading cause of mental retardation. Fetal alcohol exposure can cause numerous birth defects, most commonly effecting the craniofacial skeleton and nervous system. Fetal Alcohol Spectrum Disorder describes the full range of potential ethanol-induced birth defects and has been estimated to have a prevalence of 10 in 1000 births. The timing and concentration of fetal alcohol exposure are important determinants of FASD phenotypes. There also appears to be genetic susceptibility to FASD, yet we know almost nothing about the nature of these susceptibility loci. The zebrafish embryo is particularly useful for genetic screening and, here, we propose genetic screens to identify and characterize loci that may underlie the facial and neural defects associated with FASD.
In Aim 1, we screen zebrafish mutants ethanol-induced facial defects.
In Aim 2, we determine the neural and behavioral outcomes of these gene- ethanol interactions.
In Aim 3, we characterize the interaction between the mTOR and Hsp90 pathways in the etiology of ethanol-induced defects. Because of the conservation of gene function between zebrafish and humans, the results from our studies will provide key insights into the genetic loci that interact with ethanol to cause FASD.
Alcohol is the leading cause of preventable birth defects. Along with ethanol dosage and timing, there appear to be genetic underpinnings to alcohol-induced birth defects. Despite this fact, much remains to be learned about the genetic predispositions to ethanol-induced birth defects. Our studies will provide important insights into the mechanisms of gene-alcohol interactions. Due to the high conservation of gene function between zebrafish and human, the results we obtain will translate to human disease: providing candidate loci for association studies, risk factors for genetic counseling and potential therapies
| Tang, Xinyu; Eberhart, Johann K; Cleves, Mario A et al. (2018) PDGFRA gene, maternal binge drinking and obstructive heart defects. Sci Rep 8:11083 |
| Lovely, C; Rampersad, Mindy; Fernandes, Yohaan et al. (2017) Gene-environment interactions in development and disease. Wiley Interdiscip Rev Dev Biol 6: |
| Lovely, Charles Ben; Fernandes, Yohaan; Eberhart, Johann K (2016) Fishing for Fetal Alcohol Spectrum Disorders: Zebrafish as a Model for Ethanol Teratogenesis. Zebrafish 13:391-8 |
