Electronic Theses for Schreyer Honors College
Add My Work
Author Last Name
Area of Honors
Transcriptome Analysis of Heterozygous Rbm8a Conditional Knockout Mice
Restricted (Penn State Only)
Area of Honors:
Bachelor of Science
Yingwei Mao, Thesis Supervisor
Bernhard Luscher, Honors Advisor
RBM8A is a component of the exon junction complex (EJC), a complex of four core proteins that binds pre-mRNAs and influences their splicing, transport, and nonsense-mediated decay. Dysfunction in the core proteins has been linked to several detriments in brain development. In this study, we used next-generation RNA-sequencing to identify differentially-expressed genes (DEGs) in mice with heterozygous, conditional knockout (hcKO) of Rbm8a in the brain at embryonic day 12 and at postnatal day 17, in order to understand the functional role of Rbm8a in brain development. Additionally, we analyzed enriched gene clusters and signaling pathways within the DEGs. At the E12 time point, between the hcKO and WT mice, about 100 significant DEGs showed >2-fold change, among which we identified 19 genes related to the central nervous system (CNS). When E12 and P17 results were compared, three DEGs, Spp1, Gpnmb, and Top2a, appeared to peak at different developmental time points in the Rbm8a hcKO mice. Spp1 and Gpnmb regulate bone development, while Top2a is a DNA topoisomerase specific to embryonic CNS and participates directly in cell division. Fam212b, significantly upregulated in all tested conditions, is expressed by neuronal progenitor cells (NPCs) and postnatally expressed by immature neuronal subpopulations in the cerebrum and other limited brain regions. Further observations are necessary to determine these genes’ roles in CNS development. Enrichment analyses suggested altered activity in pathways affecting cellular proliferation, differentiation, and survival. The results support the hypothesis that loss of Rbm8a causes decreased cellular proliferation and early differentiation of neuronal subtypes, which may lead ultimately to an altered neuronal subtype composition in the brain.
Login using your Penn State access account to view the paper.