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Alliance"],"accepted":{"date-parts":[[2026,6,19]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<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-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 in vivo 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 knock-in mouse model with a CRISPR\/Cas9-mediated deletion of exon 2 in the endogenous murine\n                    <jats:italic>Sptlc1<\/jats:italic>\n                    locus. Although heterozygous mice did not develop motor defects or ALS-like neuropathology, homozygous mutants died prematurely. These findings provide valuable insights into SPTLC1 exon 2 biology and serve as a useful resource for future mechanistic studies.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202503605","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T06:21:41Z","timestamp":1781936501000},"page":"e202503605","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Deletion of exon 2 in ALS-linked\n                    <i>Sptlc1<\/i>\n                    causes lethality in homozygous mice but not in heterozygotes"],"prefix":"10.26508","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4046-4195","authenticated-orcid":true,"given":"Devesh C","family":"Pant","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cell Biology, Emory University","place":[", Atlanta, GA, 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