{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Verdone BM"],"funding":["NIA NIH HHS","The Professor Fredric Rieders, PhD scholarship","NINDS NIH HHS","National Institutes of Health","NIH HHS","Muscular Dystrophy Association"],"pagination":["5644"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8979946"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12(1)"],"pubmed_abstract":["Translation of the hexanucleotide G4C2 expansion associated with C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) produces five different dipeptide repeat protein (DPR) species that can confer toxicity. There is yet much to learn about the contribution of a single DPR to disease pathogenesis. We show here that a short repeat length is sufficient for the DPR poly-GR to confer neurotoxicity in vitro, a phenomenon previously unobserved. This toxicity is also reported in vivo in our novel knock-in mouse model characterized by widespread central nervous system (CNS) expression of the short-length poly-GR. We observe sex-specific chronic ALS/FTD-like phenotypes in these mice, including mild motor neuron loss, but no TDP-43 mis-localization, as well as motor and cognitive impairments. We suggest that this model can serve as the foundation for phenotypic exacerbation through second-hit forms of stress."],"journal":["Scientific reports"],"pubmed_title":["A mouse model with widespread expression of the C9orf72-linked glycine-arginine dipeptide displays non-lethal ALS/FTD-like phenotypes."],"pmcid":["PMC8979946"],"funding_grant_id":["RF1-NS114128","628389","RF1 AG057882","R01-NS109150","RF1 NS114128","R21-NS090912"],"pubmed_authors":["Verdone BM","Cicardi ME","Wen X","Sriramoji S","Krishnamurthy K","Trotti D","Markandaiah SS","Haeusler AR","Jensen BK","Pasinelli P","Russell K"],"additional_accession":[]},"is_claimable":false,"name":"A mouse model with widespread expression of the C9orf72-linked glycine-arginine dipeptide displays non-lethal ALS/FTD-like phenotypes.","description":"Translation of the hexanucleotide G4C2 expansion associated with C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) produces five different dipeptide repeat protein (DPR) species that can confer toxicity. There is yet much to learn about the contribution of a single DPR to disease pathogenesis. We show here that a short repeat length is sufficient for the DPR poly-GR to confer neurotoxicity in vitro, a phenomenon previously unobserved. This toxicity is also reported in vivo in our novel knock-in mouse model characterized by widespread central nervous system (CNS) expression of the short-length poly-GR. We observe sex-specific chronic ALS/FTD-like phenotypes in these mice, including mild motor neuron loss, but no TDP-43 mis-localization, as well as motor and cognitive impairments. We suggest that this model can serve as the foundation for phenotypic exacerbation through second-hit forms of stress.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2025-04-26T15:15:05.11Z","creation":"2025-04-06T14:51:05.508Z"},"accession":"S-EPMC8979946","cross_references":{"pubmed":["35379876"],"doi":["10.1038/s41598-022-09593-z"]}}