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Effects of ATRX Deficiency and/or Altered Ubiquitination on Candidate Gene Expression in Hippocampal Tissue from C57BL/6J Mice

dc.contributor.authorMacDonald, Sarah
dc.contributor.copyright-releaseNot Applicable
dc.contributor.degreeMaster of Science
dc.contributor.departmentDepartment of Psychology and Neuroscience
dc.contributor.ethics-approvalNot Applicable
dc.contributor.external-examinerN/A
dc.contributor.manuscriptsNot Applicable
dc.contributor.thesis-readerRichard Brown
dc.contributor.thesis-readerShelley Adamo
dc.contributor.thesis-supervisorIan Weaver
dc.date.accessioned2025-07-22T16:22:09Z
dc.date.available2025-07-22T16:22:09Z
dc.date.defence2025-06-24
dc.date.issued2025-07-18
dc.description.abstractThe 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.urihttps://hdl.handle.net/10222/85225
dc.language.isoen
dc.subjectATRX
dc.subjectAutism
dc.subjectLearning Impairments
dc.subjectGenetics
dc.titleEffects of ATRX Deficiency and/or Altered Ubiquitination on Candidate Gene Expression in Hippocampal Tissue from C57BL/6J Mice

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