Investigating the role of RNA-binding motif protein 8A (RBM8A, also known as Y14) in schizophrenia

Open Access
- Author:
- Harrison, Michelle Lynn
- Graduate Program:
- Genetics
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- March 28, 2013
- Committee Members:
- Yingwei Mao, Thesis Advisor/Co-Advisor
- Keywords:
- RBM8A
Y14
schizophrenia - Abstract:
- Schizophrenia is a severe mental illness which affects approximately one percent of the world’s population. While the exact cause remains unknown, we do know that it results from a combination of both genetic and environmental factors. With advancements in DNA sequencing technology, several individual genes in addition to larger chromosomal regions have been identified as schizophrenia-associated. Despite the identification of these candidate genes, the complexity of the disease has prevented the elucidation of a clear molecular mechanism. Identifying the risk factors is only the first step towards building a stronger understanding of the disease model. Given the polygenic nature of schizophrenia, it is also necessary to continue the search for additional potential risk genes. This thesis will focus on the RNA-binding motif protein 8A gene (RBM8A), commonly referred to as Y14. Although Y14 has not yet been linked to schizophrenia, our group is working to suggest that this gene is an important factor in helping to understand the disease. For this purpose, we looked at several ways in which we could manipulate the gene. First, we were able to achieve effective Y14 overexpression in vitro, which led to in vivo studies indicating that Y14 can regulate hippocampal neural development and anxiety-like behaviors in mice. Additionally, we designed a Y14 conditional knockout mouse which recently resulted in the production of eight male chimeras. Overall, the techniques employed to investigate the potential role of Y14 have provided exciting new ideas and will serve as a platform for the future study of schizophrenia and other neurological disorders.