{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Moir RD"],"funding":["NICHD NIH HHS","NINDS NIH HHS","NCI NIH HHS","National Institutes of Health","NIH HHS"],"pagination":["RP95314"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11537486"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13"],"pubmed_abstract":["Pathogenic variants in subunits of RNA polymerase (Pol) III cause a spectrum of <i>Polr3</i>-related neurodegenerative diseases including 4H leukodystrophy. Disease onset occurs from infancy to early adulthood and is associated with a variable range and severity of neurological and non-neurological features. The molecular basis of <i>Polr3</i>-related disease pathogenesis is unknown. We developed a postnatal whole-body mouse model expressing pathogenic <i>Polr3a</i> mutations to examine the molecular mechanisms by which reduced Pol III transcription results primarily in central nervous system phenotypes. <i>Polr3a</i> mutant mice exhibit behavioral deficits, cerebral pathology and exocrine pancreatic atrophy. Transcriptome and immunohistochemistry analyses of cerebra during disease progres"],"journal":["eLife"],"pubmed_title":["Molecular basis of neurodegeneration in a mouse model of &lt;i&gt;Polr3&lt;/i&gt;-related disease."],"pmcid":["PMC11537486"],"funding_grant_id":["R01 NS129951","U54 HD090260","P30 CA013330","R21 NS123730","S10 OD023591","S10 OD026852","P50 HD105352","RO1 NS129951"],"pubmed_authors":["Merheb E","Moir RD","Stanley ER","Chitu V","Willis IM"],"additional_accession":[]},"is_claimable":false,"name":"Molecular basis of neurodegeneration in a mouse model of &lt;i&gt;Polr3&lt;/i&gt;-related disease.","description":"Pathogenic variants in subunits of RNA polymerase (Pol) III cause a spectrum of <i>Polr3</i>-related neurodegenerative diseases including 4H leukodystrophy. Disease onset occurs from infancy to early adulthood and is associated with a variable range and severity of neurological and non-neurological features. The molecular basis of <i>Polr3</i>-related disease pathogenesis is unknown. We developed a postnatal whole-body mouse model expressing pathogenic <i>Polr3a</i> mutations to examine the molecular mechanisms by which reduced Pol III transcription results primarily in central nervous system phenotypes. <i>Polr3a</i> mutant mice exhibit behavioral deficits, cerebral pathology and exocrine pancreatic atrophy. Transcriptome and immunohistochemistry analyses of cerebra during disease progres","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Nov","modification":"2026-05-04T06:42:21.079Z","creation":"2025-04-06T10:11:24.392Z"},"accession":"S-EPMC11537486","cross_references":{"pubmed":["39499645"],"doi":["10.7554/eLife.95314"]}}