[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Previous research has shown a genetic variant in the serotonin transporter gene (Slc6a4) can increase the severity of a person's reaction to stress. This variant interacts with environmental stressors resulting in poorer health outcomes. Previous studies have also found that stressing pregnant mothers who carry the variant can result in an increased likelihood of autism diagnosis for the child. This maternal genotype x prenatal stress interaction has been modeled in the serotonin transporter knockout (SERT KO) mouse--dams genetically modified to mimic humans carrying the short allele were stressed during pregnancy resulting in offspring showing altered social behavior, repetitive behavior, and anxiety behavior. The first study included in this dissertation attempted to replicate this model while using a foster dam paradigm to avoid potential maternal care confounds. Surprisingly, the results showed that equalizing maternal care equalized several group differences in behavior. It is theorized that this is due to elimination of the neonatal insult from poor maternal care that would correspond to a human prenatal insult during a previously identified critical time period. The second study explored the potential effects environmentally enriched home cages on anxiety like behaviors of SERT KO mice. The study showed that all animals, regardless of genotype, showed fewer anxiety like behaviors in the open field assay. Together, these studies expand on our understanding of environmental influence on SERT KO mice used in translational studies.
Impaired hypothalamic-pituitary-adrenal axis and its feedback regulation in serotonin transporter knockout mice