{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:50:35Z","timestamp":1791845435097,"version":"4.3.4"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,3,26]]},"abstract":"<jats:p>\n                    Mutations in the Tar DNA binding protein of 43 kDa (TDP-43; TARDBP) are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43\n                    <jats:sup>+<\/jats:sup>\n                    inclusions (FTLD-TDP). To determine the physiological function of TDP-43, we knocked out zebrafish Tardbp and its paralogue Tardbp (TAR DNA binding protein-like), which lacks the glycine-rich domain where ALS- and FTLD-TDP\u2013associated mutations cluster.\n                    <jats:italic>tardbp<\/jats:italic>\n                    mutants show no phenotype, a result of compensation by a unique splice variant of\n                    <jats:italic>tardbpl<\/jats:italic>\n                    that additionally contains a C-terminal elongation highly homologous to the glycine-rich domain of\n                    <jats:italic>tardbp<\/jats:italic>\n                    . Double-homozygous mutants of\n                    <jats:italic>tardbp<\/jats:italic>\n                    and\n                    <jats:italic>tardbpl<\/jats:italic>\n                    show muscle degeneration, strongly reduced blood circulation, mispatterning of vessels, impaired spinal motor neuron axon outgrowth, and early death. In double mutants the muscle-specific actin binding protein Filamin Ca is up-regulated. Strikingly,\n                    <jats:italic>Filamin C<\/jats:italic>\n                    is similarly increased in the frontal cortex of FTLD-TDP patients, suggesting aberrant expression in smooth muscle cells and TDP-43 loss-of-function as one underlying disease mechanism.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1218311110","type":"journal-article","created":{"date-parts":[[2013,3,2]],"date-time":"2013-03-02T07:22:44Z","timestamp":1362208964000},"page":"4986-4991","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":164,"title":["Loss of ALS-associated TDP-43 in zebrafish causes muscle degeneration, vascular dysfunction, and reduced motor neuron axon outgrowth"],"prefix":"10.1073","volume":"110","author":[{"given":"Bettina","family":"Schmid","sequence":"first","affiliation":[{"name":"German Center for Neurodegenerative Diseases, 80336 Munich, Germany;"},{"name":"Adolf-Butenandt-Institute, Biochemistry, 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