{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T21:05:08Z","timestamp":1766869508396,"version":"3.41.2"},"reference-count":21,"publisher":"Wiley","issue":"11-12","license":[{"start":{"date-parts":[[2018,11,29]],"date-time":"2018-11-29T00:00:00Z","timestamp":1543449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","award":["CERG 660513","CERG 660407"],"award-info":[{"award-number":["CERG 660513","CERG 660407"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genesis"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>MAB21L2(R51C)<\/jats:italic> is one of the five documented <jats:italic>MAB21L2<\/jats:italic> mutations in human patients with bilateral eye malformations identified via whole exome sequencing. In addition to the eye abnormality, patients with <jats:italic>MAB21L2<\/jats:italic><jats:sup>\n<jats:italic>R51C\/+<\/jats:italic><\/jats:sup> mutation also have skeletal dysplasia and intellectual disability. To evaluate the pathology of this mutant allele systematically in understanding the functional role of <jats:italic>MAB21L2<\/jats:italic> in human development, we introduce the <jats:italic>R51C<\/jats:italic> mutation into the mouse genome by CRISPR\/Cas9 system to generate a mouse model for detailed characterization. The <jats:italic>Mab21l2<\/jats:italic><jats:sup>\n<jats:italic>R51C\/+<\/jats:italic><\/jats:sup> mice have eyeless phenotype and skeletal abnormalities. Micro\u2010computed tomography (micro\u2010CT) analysis showed the <jats:italic>Mab21l2<\/jats:italic><jats:sup>\n<jats:italic>R51C\/+<\/jats:italic><\/jats:sup> mice have no eye balls but with two abnormal tissues underneath the brain. Histological analysis revealed that the early eye development in the mutant embryos is interrupted. In addition, <jats:italic>Mab21l2<\/jats:italic><jats:sup>\n<jats:italic>R51C\/+<\/jats:italic><\/jats:sup> mice also have joint fusion phenotype; the humerus is fused with radius, whereas femur is fused with tibia. Limbs in the mutant animals are distinctly shorter than the wild type; and deltoid tuberosities in humeri are absent in these <jats:italic>Mab21l2<\/jats:italic><jats:sup>\n<jats:italic>R51C\/+<\/jats:italic><\/jats:sup> mice. In summary, we showed that our <jats:italic>Mab21l2<\/jats:italic><jats:sup>\n<jats:italic>R51C\/+<\/jats:italic><\/jats:sup> mutant mice have recapitulated the pathological features in eye and bone of human patients. Further analyses of the mutant phenotype with molecular markers will provide insight on how <jats:italic>MAB21L2<\/jats:italic> guides the optic differentiation and skeletogenesis, revealing specific underlying pathogenic mechanism of the <jats:italic>MAB21L2(R51C)<\/jats:italic> mutation.<\/jats:p>","DOI":"10.1002\/dvg.23261","type":"journal-article","created":{"date-parts":[[2018,10,30]],"date-time":"2018-10-30T15:19:26Z","timestamp":1540912766000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Generation and characterization of pathogenic <i>Mab21l2(R51C)<\/i> mouse model"],"prefix":"10.1002","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3860-5115","authenticated-orcid":false,"given":"Shun\u2010Wa","family":"Tsang","sequence":"first","affiliation":[{"name":"Division of Life Science The Hong Kong University of Science and Technology  Kowloon Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanjiang","family":"Guo","sequence":"additional","affiliation":[{"name":"Division of Life Science The Hong Kong University of Science and Technology  Kowloon Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long\u2010Hei","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Life Science The Hong Kong University of Science and Technology  Kowloon Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingyu","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Life Science The Hong Kong University of Science and Technology  Kowloon Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"King L.","family":"Chow","sequence":"additional","affiliation":[{"name":"Division of Life Science The Hong Kong University of Science and Technology  Kowloon Hong Kong"},{"name":"Department of Chemical and Biological Engineering The Hong Kong University of Science and Technology  Kowloon Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,29]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-5-48"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.10.010"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.093906"},{"issue":"11","key":"e_1_2_5_5_1","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.1242\/dev.121.11.3615","article-title":"The mab\u201021 gene of Caenorhabditis elegans encodes a novel protein required for choice of alternate cell fates","volume":"121","author":"Chow K. 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