{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:00:33Z","timestamp":1783422033866,"version":"3.54.6"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Trimeric intracellular potassium channels TRIC-A and -B are endoplasmic reticulum (ER) integral membrane proteins, involved in the regulation of calcium release mediated by ryanodine (RyRs) and inositol 1,4,5-trisphosphate (IP<jats:sub>3<\/jats:sub>Rs) receptors, respectively. While TRIC-A is mainly expressed in excitable cells, TRIC-B is ubiquitously distributed at moderate level. TRIC-B deficiency causes a dysregulation of calcium flux from the ER, which impacts on multiple collagen specific chaperones and modifying enzymatic activity, leading to a rare form of osteogenesis imperfecta (OI Type XIV). The relevance of TRIC-B on cell homeostasis and the molecular mechanism behind the disease are still unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, we exploited zebrafish to elucidate the role of TRIC-B in skeletal tissue. We demonstrated, for the first time, that <jats:italic>tmem38a<\/jats:italic> and <jats:italic>tmem38b<\/jats:italic> genes encoding Tric-a and -b, respectively are expressed at early developmental stages in zebrafish, but only the latter has a maternal expression. Two zebrafish mutants for <jats:italic>tmem38b<\/jats:italic> were generated by CRISPR\/Cas9, one carrying an out of frame mutation introducing a premature stop codon (<jats:italic>tmem38b<jats:sup>-\/-<\/jats:sup><\/jats:italic>) and one with an in frame deletion that removes the highly conserved KEV domain (<jats:italic>tmem38b<jats:sup>\u0394120-7\/\u0394120-7<\/jats:sup><\/jats:italic>). In both models collagen type I is under-modified and partially intracellularly retained in the endoplasmic reticulum, as described in individuals affected by OI type XIV. <jats:italic>Tmem38b<jats:sup>-\/-<\/jats:sup><\/jats:italic> showed a mild skeletal phenotype at the late larval and juvenile stages of development whereas <jats:italic>tmem38b<jats:sup>\u0394120-7\/\u0394120-7<\/jats:sup><\/jats:italic> bone outcome was limited to a reduced vertebral length at 21 dpf. A caudal fin regeneration study pointed towards impaired activity of osteoblasts and osteoclasts associated with mineralization impairment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our data support the requirement of Tric-b during early development and for bone cell differentiation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1002914","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T05:30:40Z","timestamp":1674451840000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Zebrafish Tric-b is required for skeletal development and bone cells differentiation"],"prefix":"10.3389","volume":"14","author":[{"given":"Francesca","family":"Tonelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Leoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Daponte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Gioia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Cotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imke A. 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