Date of Completion
Spring 5-2-2025
Thesis Advisor(s)
Michael J. O'Neill; Katelyn DeNegre; Eric May
Honors Major
Molecular and Cell Biology
Disciplines
Behavior and Behavior Mechanisms | Genetics | Molecular Genetics
Abstract
Sex biases are prevalent among various neurodevelopmental disorders, with males experiencing them at higher frequencies or severities than females. This male bias is poorly understood, and our lab aims to elucidate this mechanism using our model of transgenerational epigenetic inheritance. Our lab identified the cluster of genes Xlr3b/4b/4c on the X chromosome that are imprinted in the female brain. Preliminary studies suggest that Xlr3 acts as a mediator molecule in our model. Xlr3 knockdown male mice exhibited significant meiocyte loss that can be attributed to Meiotic Sex Chromosome Inactivation. Their female offspring also displayed loss of imprinting of Xlr3 and their grandsons exhibited neurodevelopmental abnormalities and behavioral deficits. This project focuses on the imprint status of control versus transgenic F1 female hybrid mice, generated from a cross between a homozygous In(X)1h mother and homozygous C57 father. Brains were collected and RNA was extracted and converted into cDNA for use in the AdamAB PCR, an allele-specific assay designed to detect Xlr3a and Xlr3b. This PCR is run out on a gel to visualize the imprint status of control and transgenic mice. The frequency of LOI was calculated for the control and transgenic mice. Results showed that the control frequency was about 20.7% and for transgenic mice was about 16.9%. Statistical analysis concluded there is insufficient evidence of a difference between the frequencies. Further research should involve age-matched and larger sample sizes and quantitative analysis for more accurate results.
Recommended Citation
Roach, Arianna H., "Examining Loss of Imprint in F1 Hybrid Female Mice Due to X Chromosome Epimutation and the Implications for Autism" (2025). Honors Scholar Theses. 1080.
https://digitalcommons.lib.uconn.edu/srhonors_theses/1080
