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Both variants in either the heterozygous or homozygous state did not impact protein expression levels of Tdp\u201043 in the central nervous system. However, homozygous G347C zebrafish displayed reduced expression levels of the\n                      <jats:italic>tardbp<\/jats:italic>\n                      transcript. We observed muscle cell atrophy starting at 1\u2009year of age and loss of large spinal cord motor neurons in both KI models in older fish (2.35\u20133\u2009years of age). We did not observe Tdp\u201043 aggregates. However, we did observe increased cytoplasmic Tdp\u201043 localization in spinal cord motor neurons in A379T zebrafish. At 1\u2009year of age, whole spinal cord RNA\u2010sequencing revealed an upregulation of neuroinflammatory transcripts in both models, as well as the selective downregulation of transcripts involved with synaptic function in G347C zebrafish, including\n                      <jats:italic>syn2a<\/jats:italic>\n                      ,\n                      <jats:italic>syn2b<\/jats:italic>\n                      ,\n                      <jats:italic>syt2a<\/jats:italic>\n                      , and\n                      <jats:italic>stxbp1a<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>These novel models of common TDP\u201043 disease variants provide a unique opportunity to further our understanding of neurodegeneration in vivo and demonstrate that mutations in the same protein and domain can manifest with different phenotypes. ANN NEUROL 2026;99:178\u2013197<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78012","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T11:21:12Z","timestamp":1756293672000},"page":"178-197","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>\n                      <i>TARDBP<\/i>\n                    <\/scp>\n                    (\n                    <scp>TDP<\/scp>\n                    \u201043) Knock\u2010in Zebrafish Display a Late\u2010Onset Motor Phenotype and Loss of Large Spinal Cord Motor Neurons"],"prefix":"10.1002","volume":"99","author":[{"given":"Ziyaan A.","family":"Harji","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurosurgery McGill University  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian J.","family":"Rampal","sequence":"additional","affiliation":[{"name":"Department of 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