{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T07:53:30Z","timestamp":1788335610253,"version":"build-2803163510"},"posted":{"date-parts":[[2026,4,12]]},"group-title":"Developmental Biology","reference-count":40,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["F31-DE033289"],"award-info":[{"award-number":["F31-DE033289"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-AR073828"],"award-info":[{"award-number":["R01-AR073828"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01-AR080896"],"award-info":[{"award-number":["R01-AR080896"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R35-GM142786"],"award-info":[{"award-number":["R35-GM142786"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R03-DE034789"],"award-info":[{"award-number":["R03-DE034789"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/0520gqb12","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/01nbasn20","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Mutations in platelet-derived growth factor receptor beta (PDGFR\u03b2) cause Kosaki overgrowth syndrome (KOGS). Patients exhibit increased linear growth, craniosynostosis, and thin skin with increased elasticity and scarring. Of the KOGS patients identified to date, three unrelated individuals carried a P584R mutation in the juxtamembrane domain of PDGFR\u03b2, resulting in constitutive receptor activation. Due to the limited number of patients, extensive phenotyping and exploration of the molecular basis of disease, including modifier genes, has not been completed. We generated conditional knock-in mice to express mouse PDGFR\u03b2 with a P583R mutation, corresponding to human P584R, under control of the endogenous\n                  <jats:italic>Pdgfrb<\/jats:italic>\n                  gene. Mutant mice were born at the expected ratio and appeared normal at birth. At 3 weeks of age, mutants began to exhibit connective tissue changes: increased body weight and bone length, craniosynostosis, ectopic bone in the tail and tendons, thin lipodystrophic skin, and high incidence of penile and rectal prolapse. To identify signaling changes caused by mutant PDGFR\u03b2 signaling, we performed western blotting and phosphoproteomics on dermal fibroblasts. This uncovered increased phosphorylation of PDGFR\u03b2, PLC\u03b3, Akt1, Shp2, STAT1, STAT2, STAT3, and STAT5. Analysis of 6,621 proteins and 5,386 phosphopeptides identified upregulation of interferon signaling genes linked to STAT1. In many cell types, STAT1 has tumor-suppressor functions and acts to inhibit cell cycle. We generated\n                  <jats:italic>Stat1<\/jats:italic>\n                  <jats:sup>-\/-<\/jats:sup>\n                  <jats:italic>Pdgfrb<\/jats:italic>\n                  <jats:sup>+\/P583R<\/jats:sup>\n                  mice to test the contribution of STAT1 to KOGS phenotypes.\n                  <jats:italic>Stat1<\/jats:italic>\n                  -deletion exacerbated overgrowth and calvaria dysmorphogensis, and caused keloid-like skin fibrosis. No phenotypes present in the original\n                  <jats:italic>Pdgfrb<\/jats:italic>\n                  <jats:sup>+\/P583R<\/jats:sup>\n                  mice were reverted to normal after\n                  <jats:italic>Stat1<\/jats:italic>\n                  deletion. Therefore, the P583R mouse model mirrored KOGS phenotypes and increased activation of multiple PDGFR\u03b2 signaling mediators; in this context, STAT1 activity opposes PDGFR\u03b2-driven overgrowth and fibrosis.\n                <\/jats:p>","DOI":"10.64898\/2026.04.09.717535","type":"posted-content","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T06:30:19Z","timestamp":1776061819000},"source":"Crossref","is-referenced-by-count":1,"title":["Connective tissue growth in a mouse model of Kosaki overgrowth syndrome is limited by STAT1"],"prefix":"10.64898","author":[{"given":"Jang H.","family":"Kim","sequence":"first","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA"},{"name":"Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Ryong","family":"Kwon","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L.","family":"Berry","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2168-7836","authenticated-orcid":false,"given":"Lorin E.","family":"Olson","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA"},{"name":"Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, 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