mRNA expression analysis of the hippocampus in a Vervet monkey model of FASD

The vervet monkey (Chlorocebus aethiops) has proven to be an invaluable tool for researching voluntary alcohol ingestion and the sequelae that can arise from such behaviour. In this study, a vervet monkey model for fetal alcohol spectrum disorder was generated by providing a cohort of alcohol preferring, pregnant dams the option to ingest alcohol between gestational days 90-165 with a corresponding sucrose matched control group. Subsequently, gene expression analysis of the hippocampus was contrasted at 5 months and 2 years using the GeneChip Rhesus Macaque Genome Array in a 2x2 study design which interrogated two independent variables, Age and Alcohol consumption. The analysis identified a global downregulation of expression when interrogating Alcohol as a main effect with a relative balance of upregulation and downregulation using Age as a main effect. Functional annotation of both independent variables was performed with Alcohol generating broad functional annotation clusters which could implicate an epigenetic role in downregulation, while Age reliably produced functional annotation clusters predominantly related to development. Furthermore, our data reveal a novel connection between EFNB1 and FASD which is highly plausible given its role in development as well as its central role in craniofrontal nasal syndrome (CFNS).

Methods
mRNA isolated from entire hippocampus of 5 month old and 2 year old Vervet monkeys. RNA hybridized to GeneChip Rhesus Macaque genome array from Affymetrix. Normalized using RMA, probe sets were trimmed using MAS5 calls (p<0.05). Only probe sets with annotations were retained.