{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T12:06:26Z","timestamp":1784376386324,"version":"3.55.0"},"posted":{"date-parts":[[2025,11,5]]},"group-title":"Genetics","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["AR078663"],"award-info":[{"award-number":["AR078663"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Dual-specificity tyrosine phosphorylation-regulated kinase 1A (\n                  <jats:italic>DYRK1A<\/jats:italic>\n                  ) is a dosage sensitive gene located on human chromosome 21 (Hsa21) that contributes to phenotypes associated with developmental disorders like Down syndrome and\n                  <jats:italic>DYRK1A<\/jats:italic>\n                  haploinsufficiency syndrome. Complete genetic knockout of\n                  <jats:italic>Dyrk1a<\/jats:italic>\n                  from conception is embryonic lethal, presenting a barrier in its study. The\n                  <jats:italic>mbk-1<\/jats:italic>\n                  gene in\n                  <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                  has been identified as an ortholog to mammalian\n                  <jats:italic>Dyrk1a<\/jats:italic>\n                  , and genetic knockout of\n                  <jats:italic>mbk-1<\/jats:italic>\n                  in\n                  <jats:italic>C. elegans<\/jats:italic>\n                  is not lethal. We hypothesized that deletion of the\n                  <jats:italic>mbk-1<\/jats:italic>\n                  gene would alter chemosensory function, learning, and motility in\n                  <jats:italic>C. elegans<\/jats:italic>\n                  , and that these phenotypes would be recovered using a humanized\n                  <jats:italic>DYRK1A<\/jats:italic>\n                  replacement at the endogenous\n                  <jats:italic>mbk-1<\/jats:italic>\n                  locus. Using behavioral preference index assays, analyses of locomotion, and learning in classical conditioning procedures, an\n                  <jats:italic>mbk-1<\/jats:italic>\n                  knockout strain of\n                  <jats:italic>C. elegans<\/jats:italic>\n                  , EK228, was characterized to identify potential behavioral roles of\n                  <jats:italic>mbk-1<\/jats:italic>\n                  . Preference index assays assessing chemosensory capabilities determined that\n                  <jats:italic>mbk-1<\/jats:italic>\n                  deletion yielded no detrimental effects. Thrashing and foraging behavior analyses uncovered significant deficits in movement in the EK228\n                  <jats:italic>C. elegans<\/jats:italic>\n                  , which were not present in two\n                  <jats:italic>mbk-1<\/jats:italic>\n                  replacement strains containing humanized\n                  <jats:italic>DYRK1A<\/jats:italic>\n                  , suggesting an essential role of\n                  <jats:italic>mbk-1<\/jats:italic>\n                  in locomotion and motility. Lastly, classical conditioning revealed no significant deficits in the abilities of the EK228 strain in forming associative connections between stimuli. Overall, these results imply functional conservation of the mbk-1\/DYRK family kinases, and provide support for the use of humanized replacement strains of\n                  <jats:italic>C. elegans<\/jats:italic>\n                  for the study of mammalian genes.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                      <jats:caption>\n                        <jats:p>Graphical Abstract (Created with BioRender)<\/jats:p>\n                      <\/jats:caption>\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"686526v2_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                    <\/jats:fig>\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Article summary<\/jats:title>\n                  <jats:p>\n                    This work provides insight into evolutionarily conserved functions of the protein kinase\n                    <jats:italic>DYRK1A,<\/jats:italic>\n                    which is linked to developmental disorders including Down syndrome and\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    syndrome.\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    with a genetic ablation of the\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    ortholog,\n                    <jats:italic>mbk-1<\/jats:italic>\n                    , were used to examine potential roles in movement, chemosensing, and associative learning and memory, and demonstrated selective deficits in thrashing and foraging locomotion that were not observed in strains with\n                    <jats:italic>mbk-1<\/jats:italic>\n                    replacement with humanized\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    at the endogenous loci. The findings indicate a role of\n                    <jats:italic>mbk-1<\/jats:italic>\n                    in\n                    <jats:italic>C. elegans<\/jats:italic>\n                    in adaptive movement, which may provide insight into some of the cellular and neural mechanisms being influenced by\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    . Understanding of the protein kinase\n                    <jats:italic>DYRK1A<\/jats:italic>\n                    may help to elucidate novel therapeutic pathways for developmental disorders.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.11.04.686526","type":"posted-content","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T20:20:24Z","timestamp":1762374024000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of\n                  <i>DYRK1A<\/i>\n                  ortholog\n                  <i>mbk-1<\/i>\n                  impairs locomotor behavior in\n                  <i>Caenorhabditis elegans<\/i>"],"prefix":"10.64898","author":[{"given":"Elysabeth","family":"Otte","sequence":"first","affiliation":[{"name":"Department of Biology, Indiana University Indianapolis, 402 N Blackford St, Indianapolis, IN 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Bratch","sequence":"additional","affiliation":[{"name":"Department of Biology, Indiana University Indianapolis, 402 N Blackford St, Indianapolis, IN 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandria","family":"Robbins","sequence":"additional","affiliation":[{"name":"Department of Biology, Indiana University Indianapolis, 402 N Blackford St, Indianapolis, IN 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9860-5037","authenticated-orcid":false,"given":"Randall J.","family":"Roper","sequence":"additional","affiliation":[{"name":"Department of Biology, Indiana University Indianapolis, 402 N Blackford St, Indianapolis, IN 46202"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, 320 W 15th St #414, Indianapolis, IN 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Goodlett","sequence":"additional","affiliation":[{"name":"Department of Psychology, Indiana University Indianapolis, 402 N Blackford St, Indianapolis, IN 46202"},{"name":"Stark Neurosciences Research Institute, Indiana University School of Medicine, 320 W 15th St #414, Indianapolis, IN 46202"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071804500646000_2025.11.04.686526v2.1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202202111RR"},{"key":"2026071804500646000_2025.11.04.686526v2.2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.18.1915"},{"key":"2026071804500646000_2025.11.04.686526v2.3","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E06-08-0668"},{"key":"2026071804500646000_2025.11.04.686526v2.4","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-019-0143-7","article-title":"Down syndrome","volume":"6","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"2026071804500646000_2025.11.04.686526v2.5","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.253"},{"key":"2026071804500646000_2025.11.04.686526v2.6","doi-asserted-by":"crossref","first-page":"19582","DOI":"10.1038\/srep19582","article-title":"Homeodomain-Interacting Protein Kinase (HPK-1) regulates stress responses and ageing in C. elegans","volume":"6","year":"2016","journal-title":"Sci Rep"},{"key":"2026071804500646000_2025.11.04.686526v2.7","unstructured":"Brody, T. 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