{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:52:30Z","timestamp":1786549950772,"version":"build-2736575974"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,9,27]],"date-time":"2017-09-27T00:00:00Z","timestamp":1506470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR062091"],"award-info":[{"award-number":["R01AR062091"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genesis"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Aggrecan (Acan), a large proteoglycan is abundantly expressed in cartilage tissue. Disruption of <jats:italic>Acan<\/jats:italic> gene causes dwarfism and perinatal lethality of homozygous mice. Because of sustained expression of <jats:italic>Acan<\/jats:italic> in the growth plate and articular cartilage, Agc<jats:sup>Cre<\/jats:sup> model has been developed for the regulated ablation of target gene in chondrocytes. In this model, the IRES\u2010CreERT\u2010Neo\u2010pgk transgene is knocked\u2010in the 3\u2032UTR of the <jats:italic>Acan<\/jats:italic> gene. We consistently noticed variable weight and size among the Agc<jats:sup>Cre<\/jats:sup> littermates, prompting us to examine the cause of this phenotype. Wild\u2010type, Cre\u2010heterozygous (Agc<jats:sup>+\/Cre<\/jats:sup>), and Cre\u2010homozygous (Agc<jats:sup>Cre\/Cre<\/jats:sup>) littermates were indistinguishable at birth. However, by 1\u2010month, Agc<jats:sup>Cre\/Cre<\/jats:sup> mice showed a significant reduction in body weight (18\u201327%) and body length (19\u201322%). Low body weight and dwarfism was sustained through adulthood and occurred in both genders. Compared with wild\u2010type and Agc<jats:sup>+\/Cre<\/jats:sup> littermates, long bones and vertebrae were shorter in Agc<jats:sup>Cre\/Cre<\/jats:sup> mice. Histological analysis of Agc<jats:sup>Cre\/Cre<\/jats:sup> mice revealed a significant reduction in the length of the growth plate and the thickness of articular cartilage. The amount of proteoglycan deposited in the cartilage of Agc<jats:sup>Cre\/Cre<\/jats:sup> mice was nearly half of the WT littermates. Analysis of gene expression indicates impaired differentiation of chondrocyte in hyaline cartilage of Agc<jats:sup>Cre\/Cre<\/jats:sup> mice. Notably, both Acan mRNA and protein was reduced by 50% in Agc<jats:sup>Cre\/Cre<\/jats:sup> mice. A strong correlation was noted between the level of Acan mRNA and the body length. Importantly, Agc<jats:sup>+\/Cre<\/jats:sup> mice showed no overt skeletal phenotype. Thus to avoid misinterpretation of data, only the Agc<jats:sup>+\/Cre<\/jats:sup> mice should be used for conditional deletion of a target gene in the cartilage tissue.<\/jats:p>","DOI":"10.1002\/dvg.23070","type":"journal-article","created":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T14:52:52Z","timestamp":1505746372000},"source":"Crossref","is-referenced-by-count":19,"title":["Dwarfism in homozygous Agc1<sup>CreERT<\/sup> mice is associated with decreased expression of aggrecan"],"prefix":"10.1002","volume":"55","author":[{"given":"Harunur","family":"Rashid","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Institute of Oral Health Research, School of Dentistry, University of Alabama at Birmingham Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery Institute of Oral Health Research, School of 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