{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:13:27Z","timestamp":1790680407580,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T00:00:00Z","timestamp":1587600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003983","name":"Iwate University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003983","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006090","name":"Center for Global Health","doi-asserted-by":"publisher","award":["29\u20101001"],"award-info":[{"award-number":["29\u20101001"]}],"id":[{"id":"10.13039\/100006090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:p>Desbuquois dysplasia (DD) type 1 is a rare skeletal dysplasia characterized by a short stature, round face, progressive scoliosis, and joint laxity. The causative gene has been identified as calcium\u2010activated nucleotidase 1 (<jats:italic>CANT1<\/jats:italic>), which encodes a nucleotidase that preferentially hydrolyzes UDP to UMP and phosphate. In this study, we generated <jats:italic>Cant1<\/jats:italic> KO mice using CRISPR\/Cas9\u2010mediated genome editing. All F0 mice possessing frameshift deletions at both <jats:italic>Cant1<\/jats:italic> alleles exhibited a dwarf phenotype. Germline transmission of the edited allele was confirmed in an F0 heterozygous mouse, and KO mice were generated by crossing of the heterozygous breeding pairs. <jats:italic>Cant1<\/jats:italic> KO mice exhibited skeletal defects, including short stature, thoracic kyphosis, and delta phalanx, all of which are observed in DD type 1 patients. The glycosaminoglycan (GAG) content and extracellular matrix space were reduced in the growth plate cartilage of mutants, and proliferating chondrocytes lost their typical flat shape and became round. Chondrocyte differentiation, especially terminal differentiation to hypertrophic chondrocytes, was impaired in <jats:italic>Cant1<\/jats:italic> KO mice. These findings indicate that CANT1 is involved in the synthesis of GAG and regulation of chondrocyte differentiation in the cartilage and contribute to a better understanding of the pathogenesis of DD type 1.<\/jats:p>","DOI":"10.1002\/2211-5463.12859","type":"journal-article","created":{"date-parts":[[2020,4,11]],"date-time":"2020-04-11T07:45:24Z","timestamp":1586591124000},"page":"1096-1103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["CANT1 deficiency in a mouse model of Desbuquois dysplasia impairs glycosaminoglycan synthesis and chondrocyte differentiation in growth plate cartilage"],"prefix":"10.1002","volume":"10","author":[{"given":"Kazuki","family":"Kodama","sequence":"first","affiliation":[{"name":"Laboratory of Laboratory Animal Science and Medicine Co\u2010Department of Veterinary Medicine Faculty of Agriculture Iwate University Morioka 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