{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:31Z","timestamp":1784557231547,"version":"3.55.0"},"reference-count":29,"publisher":"Bioscientifica","issue":"4","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,9,25]]},"abstract":"<jats:p>\n                    Genetic variants involving steroidogenic acute regulatory protein cause lipoid congenital adrenal hyperplasia, which is characterized by impaired steroidogenesis in the adrenal glands and gonads. Functional assessment of variant STAR proteins is necessary for an accurate genetic diagnosis. Ideally, steroidogenic cells should be used to assess the functionality of STAR proteins, but the presence of endogenous STARs in steroidogenic cells precludes such a method. Here, we generated\n                    <jats:italic>Star<\/jats:italic>\n                    -edited cells from steroidogenic Y1 mouse adrenocortical tumor cells by genome editing.\n                    <jats:italic>Star<\/jats:italic>\n                    -edited Y1 cells exhibited very low but measurable cAMP-dependent pregnenolone production. Furthermore, stimulation of the cAMP pathway for 2 weeks resulted in the formation of lipid droplets in the cytoplasm of\n                    <jats:italic>Star<\/jats:italic>\n                    -edited Y1 cells, which resembled the histology of the adrenal glands of patients with lipoid congenital adrenal hyperplasia. The steroidogenic defect of\n                    <jats:italic>Star<\/jats:italic>\n                    -edited Y1 cells can be restored by transient overexpression of mouse Star. We found that human STAR can also restore defective steroidogenesis in\n                    <jats:italic>Star<\/jats:italic>\n                    -edited Y1 cells, and we were able to construct a novel\n                    <jats:italic>in vitro<\/jats:italic>\n                    system to evaluate human STAR variants. Collectively, we established\n                    <jats:italic>Star<\/jats:italic>\n                    -edited Y1 cells that retain the steroidogenic pathway downstream of the Star protein.\n                    <jats:italic>Star<\/jats:italic>\n                    -edited Y1 cells recapitulate the functional and morphological changes of lipoid congenital adrenal hyperplasia and can be used to evaluate the functionality of human STAR variants.\n                  <\/jats:p>","DOI":"10.1530\/jme-24-0009","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T14:15:04Z","timestamp":1727273704000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":0,"title":["Establishment of Star-edited Y1 cells as a novel in vitro functional assay for STAR"],"prefix":"10.1530","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0535-2975","authenticated-orcid":true,"given":"Takeshi","family":"Sato","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Narumi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsushi","family":"Sakuma","sequence":"additional","affiliation":[{"name":"Graduate School of Agriculture, Kyoto University, c\/o Regional Fish Institute, Ltd., Creation Core Kyoto Mikuruma, Kamigyo-ku, Kyoto-shi, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Shimura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Ichihashi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Division of Integrated Sciences for Life, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima-shi, Hiroshima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonobu","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Journal of Biological Chemistry","first-page":"32656","article-title":"Phosphorylation of steroidogenic acute regulatory protein (StAR) modulates its steroidogenic activity","volume":"272","author":"Arakane","year":"1997","unstructured":"Arakane FKing SRDu YKallen CBWalsh LPWatari HStocco DM & Strauss JF3rd 1997 Phosphorylation of steroidogenic acute regulatory protein (StAR) modulates its steroidogenic activity. 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