{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:06:16Z","timestamp":1768503976071,"version":"3.49.0"},"posted":{"date-parts":[[2023,2,22]]},"group-title":"Genetics","reference-count":34,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,2,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  DOCK (dedicator of cytokinesis) is an 11-member family of typical guanine nucleotide exchange factors (GEFs) expressed in the brain, spinal cord, and skeletal muscle. Several DOCK proteins have been implicated in maintaining several myogenic processes such as fusion. We previously identified DOCK3 as being strongly upregulated in Duchenne muscular dystrophy (DMD), specifically in the skeletal muscles of DMD patients and dystrophic mice.\n                  <jats:italic>Dock3<\/jats:italic>\n                  ubiquitous KO mice on the dystrophin-deficient background exacerbated skeletal muscle and cardiac phenotypes. We generated\n                  <jats:italic>Dock3<\/jats:italic>\n                  conditional skeletal muscle knockout mice (\n                  <jats:italic>Dock3<\/jats:italic>\n                  mKO) to characterize the role of DOCK3 protein exclusively in the adult muscle lineage.\n                  <jats:italic>Dock3<\/jats:italic>\n                  mKO mice presented with significant hyperglycemia and increased fat mass, indicating a metabolic role in the maintenance of skeletal muscle health.\n                  <jats:italic>Dock3<\/jats:italic>\n                  mKO mice had impaired muscle architecture, reduced locomotor activity, impaired myofiber regeneration, and metabolic dysfunction. We identified a novel DOCK3 interaction with SORBS1 through the C-terminal domain of DOCK3 that may account for its metabolic dysregulation. Together, these findings demonstrate an essential role for DOCK3 in skeletal muscle independent of DOCK3 function in neuronal lineages.\n                <\/jats:p>","DOI":"10.1101\/2023.02.22.529576","type":"posted-content","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T20:05:11Z","timestamp":1677096311000},"source":"Crossref","is-referenced-by-count":2,"title":["DOCK3 regulates normal skeletal muscle regeneration and glucose metabolism"],"prefix":"10.64898","author":[{"given":"Adrienne","family":"Samani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muthukumar","family":"Karuppasamy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine G.","family":"English","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin A.","family":"Siler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yimin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey J.","family":"Widrick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7406-5171","authenticated-orcid":false,"given":"Matthew S.","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023030804001746000_2023.02.22.529576v2.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz1776"},{"key":"2023030804001746000_2023.02.22.529576v2.2","doi-asserted-by":"publisher","DOI":"10.1038\/35025089"},{"key":"2023030804001746000_2023.02.22.529576v2.3","doi-asserted-by":"crossref","unstructured":"Beedle, A. M. (2016). \u201cCryosectioning of Contiguous Regions of a Single Mouse Skeletal Muscle for Gene Expression and Histological Analyses.\u201d (118): e55058.","DOI":"10.3791\/55058"},{"issue":"14","key":"2023030804001746000_2023.02.22.529576v2.4","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1007\/s00018-005-5029-z","article-title":"The Rho family of small GTPases: crucial regulators of skeletal myogenesis","volume":"62","year":"2005","journal-title":"Cellular and Molecular Life Sciences CMLS"},{"key":"2023030804001746000_2023.02.22.529576v2.5","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600757R"},{"issue":"1","key":"2023030804001746000_2023.02.22.529576v2.6","doi-asserted-by":"crossref","first-page":"10574","DOI":"10.1038\/s41598-018-28891-z","article-title":"Genetic variation of SORBS1 gene is associated with glucose homeostasis and age at onset of diabetes: A SAPPHIRe Cohort Study","volume":"8","year":"2018","journal-title":"Scientific Reports"},{"key":"2023030804001746000_2023.02.22.529576v2.7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3985-08.2009"},{"key":"2023030804001746000_2023.02.22.529576v2.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2011.05.022"},{"key":"2023030804001746000_2023.02.22.529576v2.9","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00219"},{"key":"2023030804001746000_2023.02.22.529576v2.10","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-S302"},{"issue":"9","key":"2023030804001746000_2023.02.22.529576v2.11","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1038\/nprot.2008.142","article-title":"Isolation of a slowly adhering cell fraction containing stem cells from murine skeletal muscle by the preplate technique","volume":"3","year":"2008","journal-title":"Nat. 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Velinov (2017). \u201cBiallelic loss-of-function variants in DOCK3 cause muscle hypotonia, ataxia, and intellectual disability.\u201d Clinical Genetics: n\/a-n\/a.","DOI":"10.1111\/cge.12995"},{"issue":"9","key":"2023030804001746000_2023.02.22.529576v2.14","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1093\/hmg\/ddy068","article-title":"SPEG-deficient skeletal muscles exhibit abnormal triad and defective calcium handling","volume":"27","year":"2018","journal-title":"Human Molecular Genetics"},{"issue":"1","key":"2023030804001746000_2023.02.22.529576v2.15","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/ajmg.a.38517","article-title":"DOCK3-related neurodevelopmental syndrome: Biallelic intragenic deletion of DOCK3 in a boy with developmental delay and hypotonia","volume":"176","year":"2018","journal-title":"American Journal of Medical Genetics Part A"},{"key":"2023030804001746000_2023.02.22.529576v2.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805546105"},{"key":"2023030804001746000_2023.02.22.529576v2.17","doi-asserted-by":"publisher","DOI":"10.1038\/nm1550"},{"issue":"4","key":"2023030804001746000_2023.02.22.529576v2.18","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1007\/s12035-015-9406-9","article-title":"Dock3 Participate in Epileptogenesis Through rac1 Pathway in Animal Models","volume":"53","year":"2016","journal-title":"Molecular Neurobiology"},{"issue":"1","key":"2023030804001746000_2023.02.22.529576v2.19","doi-asserted-by":"crossref","first-page":"5951","DOI":"10.1038\/ncomms6951","article-title":"Tropomodulin3 is a novel Akt2 effector regulating insulin-stimulated GLUT4 exocytosis through cortical actin remodeling","volume":"6","year":"2015","journal-title":"Nature Communications"},{"key":"2023030804001746000_2023.02.22.529576v2.20","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.144.5.1001"},{"key":"2023030804001746000_2023.02.22.529576v2.21","doi-asserted-by":"publisher","DOI":"10.1242\/dev.001214"},{"key":"2023030804001746000_2023.02.22.529576v2.22","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01022.2012"},{"key":"2023030804001746000_2023.02.22.529576v2.23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311275200"},{"key":"2023030804001746000_2023.02.22.529576v2.24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914514107"},{"key":"2023030804001746000_2023.02.22.529576v2.25","doi-asserted-by":"crossref","unstructured":"Noviello, C. , K. Kobon , L. Delivry , T. Guilbert , F. Julienne , P. Maire , V. Randrianarison-Huetz and A. Sotiropoulos (2021). \u201cRhoA within myofibers controls satellite cell microenvironment to allow hypertrophic growth.\u201d bioRxiv: 2021.2001.2018.426685.","DOI":"10.1101\/2021.01.18.426685"},{"key":"2023030804001746000_2023.02.22.529576v2.26","doi-asserted-by":"publisher","DOI":"10.1113\/JP275602"},{"key":"2023030804001746000_2023.02.22.529576v2.27","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaa173"},{"key":"2023030804001746000_2023.02.22.529576v2.28","doi-asserted-by":"crossref","unstructured":"Reid, A. L. , Y. Wang , A. Samani , R. M. Hightower , M. A. Lopez , S. R. Gilbert , L. Ianov , D. K. Crossman , L. J. Dell\u2019Italia , D. P. Millay , T. van Groen , G. V. Halade and M. S. 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