{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T18:43:59Z","timestamp":1775933039976,"version":"3.50.1"},"posted":{"date-parts":[[2025,2,23]]},"group-title":"Neuroscience","reference-count":22,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T00:00:00Z","timestamp":1740268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Mutations in the human\n                  <jats:italic>SPTLC1<\/jats:italic>\n                  gene have recently been linked to early onset amyotrophic lateral sclerosis (ALS), characterized by global atrophy, motor impairments, and symptoms such as tongue fasciculations. All known ALS\n                  <jats:italic>-<\/jats:italic>\n                  linked\n                  <jats:italic>SPTLC1<\/jats:italic>\n                  mutations cluster within exon 2 and a specific variant, c.58G&gt;T, results in exon 2 skipping. However, it is unclear how the exon 2 deletion affects SPTLC1 function\n                  <jats:italic>in vivo<\/jats:italic>\n                  and contributes to ALS pathogenesis. Leveraging the high genomic sequence similarity between mouse and human\n                  <jats:italic>SPTLC1<\/jats:italic>\n                  , we created a novel mouse model with a CRISPR\/Cas9-mediated deletion of exon 2 in the endogenous murine\n                  <jats:italic>Sptlc1<\/jats:italic>\n                  locus. While heterozygous mice did not develop motor defects or ALS-like neuropathology, homozygous mutants died prematurely. These findings indicate that\n                  <jats:italic>Sptlc1<\/jats:italic>\n                  \u0394Exon2 heterozygous mice do not replicate the disease phenotype but provide valuable insights into SPTLC1 biology and serve as a useful resource for future mechanistic studies.\n                <\/jats:p>","DOI":"10.1101\/2025.02.18.638951","type":"posted-content","created":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T14:20:18Z","timestamp":1740320418000},"source":"Crossref","is-referenced-by-count":0,"title":["Lack of motor defects and ALS-like neuropathology in heterozygous\n                  <i>Sptlc1<\/i>\n                  Exon 2 deletion mice"],"prefix":"10.64898","author":[{"given":"Devesh C.","family":"Pant","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Emory University, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Museer A.","family":"Lone","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry, University of Zurich, Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janani","family":"Parameswaran","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuying","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prisha","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zitong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaekeun","family":"Park","sequence":"additional","affiliation":[{"name":"Center for Systems Imaging Core, Emory University, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sumit","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neurology, Emory University, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thorsten","family":"Hornemann","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry, University of Zurich, Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041110534918000_2025.02.18.638951v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-023-00592-y"},{"key":"2026041110534918000_2025.02.18.638951v1.2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2023-331753"},{"key":"2026041110534918000_2025.02.18.638951v1.3","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2021.2598"},{"issue":"9","key":"2026041110534918000_2025.02.18.638951v1.4","first-page":"159359","article-title":"SPTLC1 p.Leu38Arg, a novel mutation associated with childhood ALS","volume":"1868","year":"2023","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"key":"2026041110534918000_2025.02.18.638951v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01346-1"},{"issue":"1","key":"2026041110534918000_2025.02.18.638951v1.6","first-page":"36","article-title":"Genetic and functional analyses of SPTLC1 in juvenile amyotrophic lateral 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