{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:56:21Z","timestamp":1793130981976,"version":"4.5.0"},"reference-count":69,"publisher":"American Society for Clinical Investigation","issue":"20","funder":[{"name":"Baltimore Center for Musculoskeletal Science","award":["80038354"],"award-info":[{"award-number":["80038354"]}]},{"DOI":"10.13039\/100013030","name":"William and Ella Owens Medical Research Foundation","doi-asserted-by":"crossref","award":["125662"],"award-info":[{"award-number":["125662"]}],"id":[{"id":"10.13039\/100013030","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Johns Hopkins School of Medicine Clinician Scientist Award","award":["80041241"],"award-info":[{"award-number":["80041241"]}]},{"DOI":"10.13039\/100006792","name":"The Hartwell Foundation","doi-asserted-by":"crossref","award":["126020"],"award-info":[{"award-number":["126020"]}],"id":[{"id":"10.13039\/100006792","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1K08HD086250-01A1"],"award-info":[{"award-number":["1K08HD086250-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"crossref","award":["DP5OD017877"],"award-info":[{"award-number":["DP5OD017877"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Louma G. Foundation","award":["Private"],"award-info":[{"award-number":["Private"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,17]]},"abstract":"<jats:p>\n                    Kabuki syndrome 1 (KS1) is a Mendelian disorder of the epigenetic machinery caused by mutations in the gene encoding KMT2D, which methylates lysine 4 on histone H3 (H3K4). KS1 is characterized by intellectual disability, postnatal growth retardation, and distinct craniofacial dysmorphisms. A mouse model (\n                    <jats:italic>Kmt2d<\/jats:italic>\n                    <jats:sup>\n                      +\/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      Geo\n                    <\/jats:sup>\n                    <jats:italic\/>\n                    ) exhibits features of the human disorder and has provided insight into other phenotypes; however, the mechanistic basis of skeletal abnormalities and growth retardation remains elusive. Using high-resolution micro-CT, we show that\n                    <jats:italic>Kmt2d<\/jats:italic>\n                    <jats:sup>\n                      +\/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      Geo\n                    <\/jats:sup>\n                    <jats:italic\/>\n                    mice have shortened long bones and ventral bowing of skulls. In vivo expansion of growth plates within skulls and long bones suggests disrupted endochondral ossification as a common disease mechanism. Stable chondrocyte cell lines harboring inactivating mutations in\n                    <jats:italic>Kmt2d<\/jats:italic>\n                    exhibit precocious differentiation, further supporting this mechanism. A known inducer of chondrogenesis, SOX9, and its targets show markedly increased expression in\n                    <jats:italic>\n                      Kmt2d\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    chondrocytes. By transcriptome profiling, we identify\n                    <jats:italic>Shox2<\/jats:italic>\n                    as a putative KMT2D target. We propose that decreased KMT2D-mediated H3K4me3 at\n                    <jats:italic>Shox2<\/jats:italic>\n                    releases\n                    <jats:italic>Sox9<\/jats:italic>\n                    inhibition and thereby leads to enhanced chondrogenesis, providing a potentially novel and plausible explanation for precocious chondrocyte differentiation. Our findings provide insight into the pathogenesis of growth retardation in KS1 and suggest therapeutic approaches for this and related disorders.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.129380","type":"journal-article","created":{"date-parts":[[2019,9,26]],"date-time":"2019-09-26T15:28:55Z","timestamp":1569511735000},"source":"Crossref","is-referenced-by-count":48,"title":["Precocious chondrocyte differentiation disrupts skeletal growth in Kabuki syndrome mice"],"prefix":"10.1172","volume":"4","author":[{"given":"Jill A.","family":"Fahrner","sequence":"first","affiliation":[{"name":"McKusick-Nathans Institute of Genetic Medicine,"},{"name":"Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Ying","family":"Lin","sequence":"additional","affiliation":[{"name":"McKusick-Nathans Institute of Genetic 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