Effects of ATRX Deficiency and/or Altered Ubiquitination on Candidate Gene Expression in Hippocampal Tissue from C57BL/6J Mice
dc.contributor.author | MacDonald, Sarah | |
dc.contributor.copyright-release | Not Applicable | |
dc.contributor.degree | Master of Science | |
dc.contributor.department | Department of Psychology and Neuroscience | |
dc.contributor.ethics-approval | Not Applicable | |
dc.contributor.external-examiner | N/A | |
dc.contributor.manuscripts | Not Applicable | |
dc.contributor.thesis-reader | Richard Brown | |
dc.contributor.thesis-reader | Shelley Adamo | |
dc.contributor.thesis-supervisor | Ian Weaver | |
dc.date.accessioned | 2025-07-22T16:22:09Z | |
dc.date.available | 2025-07-22T16:22:09Z | |
dc.date.defence | 2025-06-24 | |
dc.date.issued | 2025-07-18 | |
dc.description.abstract | The autism-risk gene Atrx encodes the chromatin-remodeling protein ATRX, which regulates histone ubiquitination and gene expression. Clariom™ assays were used to determine the effects of ATRX deficiency and ubiquitination disruption on hippocampal transcription in adult male mice. ATRX deficiency and RING1Bi-mediated ubiquitination inhibition resulted in genome-wide downregulation of memory-related genes, which was partially reversed by USP10 inhibition. Candidate genes were selected from Clariom™ assay STRING analysis. RT-qPCR analyses of mRNA levels for Brap, Crh, Gnrh1, Kras, Nr4a1, Pomc, and Prkcd aligned with the Clariom™ assay results. ELISAs revealed altered protein levels of GNRH1, KRAS, and PRKCD (but not NR4A1) in the ATRX-deficient and ubiquitination-disrupted mice. Increased hippocampal KRAS levels correlated with impaired spatial learning and memory in the Morris water maze. These findings highlight potential mechanistic pathways and upstream targets-such as Brap, Crh, Gnrh1, Kras, Nr4a1, Pomc, and Prkcd-for future studies into gene regulation underlying autism-related cognitive dysfunction. | |
dc.identifier.uri | https://hdl.handle.net/10222/85225 | |
dc.language.iso | en | |
dc.subject | ATRX | |
dc.subject | Autism | |
dc.subject | Learning Impairments | |
dc.subject | Genetics | |
dc.title | Effects of ATRX Deficiency and/or Altered Ubiquitination on Candidate Gene Expression in Hippocampal Tissue from C57BL/6J Mice |