Genetics and Genomics Commons^™

Hippocampal Epigenetic Changes In A Mouse Model Of Fetal Alcohol Spectrum Disorders, Eric J. Chater-Diehl

Electronic Thesis and Dissertation Repository

Fetal alcohol spectrum disorders (FASD) refers to the neurological, developmental, and behavioural abnormalities arising from in utero ethanol exposure. These abnormities included attention deficit, anxiety, and learning and memory impairment persisting into adulthood. The molecular mechanisms of such persistent behavioural changes remain unknown and are an area of intense research. In this thesis, mice were exposed to ethanol during the third trimester equivalent, the peak of synaptic development. Following this exposure, genome-wide epigenetic and gene expression and changes in the hippocampus were assessed in adult (70 day old) mice.

In the first experiment, genome-wide trimethylation of histone H3 at histone …

A Long-Term Neuroepigenomic Profile Of Prenatal Alcohol Exposure, Benjamin I. Laufer

Electronic Thesis and Dissertation Repository

Fetal Alcohol Spectrum Disorders (FASD) represent the largest preventable cause of cognitive deficits in the western world. The mechanism(s) of how prenatal alcohol exposure (PAE) results in FASD remain unknown. Towards this end, mouse models of PAE have successfully recreated endophenotypes that are characteristic of FASD. This doctoral thesis examines the long-term epigenomic alterations associated with PAE. I have examined both mice with PAE and human patients with FASD.

In the first set of experiments, mice with PAE and matched controls were raised to adulthood and then their whole brains were examined for alterations to gene expression, non-coding RNA (ncRNA) …

Cellular Adaptation Of Macrophages To Anthrax Lethal Toxin-Induced Pyroptosis Via Epigenetic Mechanisms, Chae Young Han

Electronic Thesis and Dissertation Repository

Cellular adaptation to microbial stresses has been demonstrated in several cell types. Macrophages (MФ) are sentinel immune cells fending off invading microbes. Anthrax lethal toxin (LeTx) is a key virulence factor released by Bacillus anthracis that causes rapid cell death, pyroptosis. A small number of RAW246.7 macrophages (~4%) exposed to a non-lethal dose of LeTx become resistant to LeTx-induced pyroptosis for ~ 4 weeks, termed “toxin-induced resistance (TIR)”. Here, I showed that high levels of DNA methyl transferase1 (DNMT1) expression were maintained although global genomic methylation levels were not high in TIR. TIR cells treated with the DNMT inhibitor 5-azacitidine …