{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T19:12:50Z","timestamp":1780686770022,"version":"3.54.1"},"reference-count":79,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":76,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000406","name":"Neuron Disease Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000406","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017510","name":"UK Dementia Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017510","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A GGGGCC repeat expansion in C9orf72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The repeat expansion is translated into five different dipeptide repeat proteins: poly(glycine-alanine) (polyGA), poly(glycine-proline) (polyGP), poly(glycine-arginine) (polyGR), poly(alanine-proline) (polyAP) and poly(proline-arginine) (polyPR). To investigate the effect of polyGA, which is the most abundant dipeptide repeat protein in patient brains, we used clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated nuclease 9 (Cas9) to insert 400 codon-optimized polyGA repeats immediately downstream of the mouse C9orf72 start codon. This generated (GA)400 knock-in mice driven by the endogenous mouse C9orf72 promoter, coupled with heterozygous C9orf72 reduction. PolyGA remains soluble up to 18 months of age and (GA)400 mice develop subtle dysfunction characterized by impaired rotarod performance, without overt neuropathological alterations. Quantitative proteomics revealed polyGA expression caused protein alterations in the spinal cord, including changes in previously identified polyGA interactors. Our findings show that (GA)400 mice are a complementary in vivo model to better understand C9orf72 ALS\/FTD pathology and determine the specific role of individual DPRs in disease.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag087","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T04:36:59Z","timestamp":1773808619000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>C9orf72<\/i>\n                    poly(glycine-alanine) knock-in mice exhibit mild rotarod and proteomic changes consistent with amyotrophic lateral sclerosis\/frontotemporal dementia"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3844-0728","authenticated-orcid":false,"given":"Carmelo","family":"Milioto","sequence":"first","affiliation":[{"name":"UK Dementia Research Institute at UCL, University College London , London WC1E 6BT ,","place":["UK"]},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]},{"name":"Dipartimento di Scienze Farmacologiche e Biomolecolari \u2018Rodolfo Paoletti\u2019, University of Milan , Milan20133 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireia","family":"Carcol\u00e9","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL, University College London , London WC1E 6BT ,","place":["UK"]},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3343-1547","authenticated-orcid":false,"given":"Matteo","family":"Zanovello","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mhoriam","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raja S","family":"Nirujogi","sequence":"additional","affiliation":[{"name":"Aligning Science Across Parkinson\u2019s (ASAP) Collaborative Research Network , Chevy Chase, MD 20815 ,","place":["USA"]},{"name":"Medical Research Council (MRC) Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee , Dundee DD1 5EH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Biggs","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Human Genetics, University of Oxford , Oxford OX3 7BN ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha J","family":"Roberts","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL, University College London , London WC1E 6BT ,","place":["UK"]},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6721-9620","authenticated-orcid":false,"given":"Kyra","family":"Schweers","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL, University College London , London WC1E 6BT ,","place":["UK"]},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J","family":"Cammack","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL, University College London , London WC1E 6BT ,","place":["UK"]},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8893-3790","authenticated-orcid":false,"given":"Paolo M","family":"Marchi","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL, University College London , London WC1E 6BT ,","place":["UK"]},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Katona","sequence":"additional","affiliation":[{"name":"UK Dementia Research Institute at UCL, University College London , London WC1E 6BT ,","place":["UK"]},{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology , London WC1N 3BG 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Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anny","family":"Devoy","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7554-1632","authenticated-orcid":false,"given":"Pietro","family":"Fratta","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]},{"name":"UCL Queen Square Motor Neuron Disease Centre, UCL Queen Square Institute of Neurology, University College London , London WC1N 3BG ,","place":["UK"]},{"name":"Francis Crick Institute , London NW1 1AT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario R","family":"Alessi","sequence":"additional","affiliation":[{"name":"Aligning Science Across Parkinson\u2019s (ASAP) Collaborative Research Network , Chevy Chase, MD 20815 ,","place":["USA"]},{"name":"Medical Research Council (MRC) Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee , Dundee DD1 5EH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Davies","sequence":"additional","affiliation":[{"name":"Wellcome Centre for Human Genetics, University of Oxford , Oxford OX3 7BN ,","place":["UK"]},{"name":"Francis Crick Institute , London NW1 1AT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Greensmith","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology , London WC1N 3BG ,","place":["UK"]},{"name":"UCL Queen Square Motor Neuron Disease Centre, UCL Queen Square Institute of 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,","place":["UK"]},{"name":"UCL Queen Square Motor Neuron Disease Centre, UCL Queen Square Institute of Neurology, University College London , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"issue":"2","key":"2026060514564584600_fcag087-B1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","article-title":"Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS","volume":"72","author":"DeJesus-Hernandez","year":"2011","journal-title":"Neuron"},{"issue":"2","key":"2026060514564584600_fcag087-B2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","article-title":"A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked 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